Fetal growth retardation and increased placental weight in the spontaneously hypertensive rat

Epidemiological studies have linked low birth weight and increased placental weight with increased risk of hypertension in adult life. It has been proposed that the cardiovascular changes which lead to hypertension are initiated in utero by processes associated with intrauterine growth retardation. The alternative possibility, that hypertension may result from genetic influences which also determine fetal and placental size, has had less support because birth weight is not determined genetically in humans. However, in the spontaneously hypertensive rat (SHR) essential hypertension is known to be transmitted genetically. Fetal and placental weights were, therefore, measured at Day 20 gestation in SHRs and compared with those in the normotensive Wistar Kyoto (WKY) control strain. Fetal weight (1.93 +/- 0.04 g) was significantly (P < 0.001) reduced in SHRs compared with WKY fetuses (2.23 +/- 0.01 g) but placental weight was heavier (P < 0.001) in SHRs (0.347 +/- 0.005 g) than in WKY rats (0.300 +/- 0.006 g) although litter size was not different. As expected, maternal blood pressure recorded under 1% halothane anaesthesia was higher (126 +/- 2.7 mm Hg) in SHR than WKY rats (100 +/- 2.1 mm Hg; 1 mm Hg = 133 Pa). In addition the concentration of maternal blood glucose in SHR was significantly (P < 0.001) higher (4.8 +/- 0.32 mM v. 3.7 +/- 0.11 mM) and the concentration of plasma insulin was significantly (P < 0.05) lower in SHRs (18.8 +/- 3.0 ng mL-1) than in WKY dams (29.4 +/- 3.1 ng mL-1). Thus, the data support human population studies which show an association between adult hypertension and a reduced fetal:placental weight ratio at birth. However, because hypertension in the SHR is genetically determined, these data suggest that fetal growth retardation and increased placental weight may also be determined genetically.     

Performance of some diagnostic systems in the prediction of occlusal caries in permanent molars in 6- and 11-year-old children

Until late in gestation, fetal spontaneously hypertensive rat (SHR) is growth retarded. Fetal growth rate increases after placental hypertrophy occurs between fetal days 18 and 20. The increase in placental mass may result in improved transfer of macro nutrients to the fetus and thus stimulate growth. In this study, fetal and placental uptake of the glucose analog 3-O-methyl glucose (3MG) and the amino acid analog amino-isobutyric acid (AIB) from the maternal circulation were compared in the SHR and Wistar-Kyoto (WKY) on days 16, 20 and 22 of gestation. Placental 3MG uptake (d/min/g tissue wet weight) was decreased in the SHR on days 20 and 22 but no differences were observed in fetal 3MG uptake. Increased placental mass in the SHR meant that total placental 3MG uptake was greater in the SHR. Placental uptake of AIB (d/min/g tissue wet weight) was much lower in the SHR (on days 16, 20 and 22) and the decrease was not compensated for by increased placental mass. Fetal uptake of AIB was decreased on days 20 and 22 (P<0.05). AIB uptake (d/min/g tissue wet weight) by the carcass and the internal organs (brain, heart, kidney, liver and lung) was also lower in the SHR. These findings indicate that although fetal growth in the SHR increases rapidly in late gestation following placental hypertrophy, it does so despite a pronounced deficit in amino acid uptake.     

Increase of the background human exposure to mercury through fish consumption due to gold mining at the Tapajós River region, Pará State, Amazon

Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant status were investigated in hypertensive, 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Total plasma calcium and magnesium concentrations were similar between both rat strains; however, systolic blood pressure in SHR was greater than in WKY at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio compared with WKY counterparts. No significant differences in the relative proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY. Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were similar in SHR and WKY counterparts. A possible compensatory effect to the oxidative status of SHR was suggested by the significant (p < 0.05) increase in both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities. Despite these results, in vitro oxidative challenge studies with H2O2 demonstrated a greater susceptibility of liver to GSH depletion in the SHR, although no parallel change in thiobarbituric acid reactive substances (TBARS) production was observed. The comparatively lower plasma cholesterol observed in hypertensive SHR paralleled specific differences in liver catalase and glutathione redox antioxidant enzyme activities.     

Ontogeny of insulin-like growth factors (IGF), IGF binding proteins, IGF receptors, and growth hormone receptor mRNA levels in porcine pancreas

We examined the ontogeny of mRNA levels of IGF-I and -II, IGF type 1 (IGFI-R) and type II receptors (IGFII-R), IGF binding protein-1 and -3 (IGFBP-1 and -3), GH receptor (GHR), and tissue concentrations of IGF and IGFBP in the pancreas of pigs. Tissues were collected from fetuses at 90 and 110 d of gestation and from pigs at 1, 21, 90 and 180 d of age. Northern blots were performed using total RNA hybridized with 32P-labeled cDNA probes (human IGF-I and human IGFI-R) and cRNA probes (rat IGF-II, human IGFII-R, human IGFBP-1, pig IGFBP-3, and pig GHR). There were two accelerated growth stages of the pancreas: the first one at 90 d of fetal life, which is characterized by cell hyperplasia (high ratio of DNA to body weight), and the second one at postnatal 90 d, which is attributed to cell hypertrophy (high ratios of pancreatic weight, RNA, and protein to DNA). The level of IGF-II mRNA and its tissue concentration were predominant during fetal life and low thereafter. The IGF-I mRNA level was high during fetal and early postnatal life and decreased thereafter. Messenger RNA levels of IGFI-R, IGFBP-3, and GHR and concentrations of IGFBP-1 and -2 were abundant during fetal and early postnatal life. In conclusion, IGF may be involved in various physiological periods of pancreatic development in pigs.     

Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.     

Effect of cross-fostering on neonatal sodium balance and adult blood pressure in the spontaneously hypertensive rat

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams' milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 +/- 2.0 to 15.2 +/- 1.2 mmol/L; SHR 31.9 +/- 2.5 to 18.2 +/- 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P < 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P < 0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4-15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 +/- 3.6 vs 59.7 +/- 2.6 mumol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 +/- 7.0 mumol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 +/- 6.4 vs 200.1 +/- 9.5 mumol/g bodyweight, respectively; P < 0.05) or SHRX pups (200.0 +/- 18.0 mumol/g bodyweight; P < 0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

Increase in affinity and loss of 5-hydroxytryptamine2A-receptor reserve for 5-hydroxytryptamine on the aorta of spontaneously hypertensive rats

1. The aim of this study was to determine whether the KA value and fractional occupancy-response relationship for 5-hydroxytryptamine (5-HT) at 5-HT2A-receptors were altered in a rat model of genetic hypertension. Thus, the effects of phenoxybenzamine, an irreversible blocker at 5-HT2A-receptors, on the responses of the aorta from spontaneously hypertensive rats (SHRs) and normotensive rats to 5-HT have been examined. The two strains of normotensive rats used were Wistar Kyoto (WKY) rats and Wistar rats bred in Auckland (WA rats). 2. The sensitivity to 5-HT was increased in aortae from hypertensive rats. The pD2 values for 5-HT during the first challenge were 5.54 +/- 0.08 (14), 5.43 +/- 0.05 (12) and 6.08 +/- 0.04 (12) on the aorta of WKY rats, WA rats, and SHRs, respectively. 3. The affinity for 5-HT was increased in hypertension. Phenoxybenzamine at 2 x 10(-8)M for 30 min caused nonparallel rightward shifts of 5-HT response curves and the KA values were 16.8 x 10(-6)M, 45.6 x 10(-6)M and 4.4 x 10(-6)M on the WKY rat, WA rat, and SHR aorta, respectively. 4. There was a loss of receptor reserve for 5-HT in aortae from hypertensive rats. On the WKY and WA rat aortae, 5-HT caused 50 and 95% maximal responses by occupying 10-20 and 45-60%, whereas on the SHR aorta 5-HT produced 50 and 95% maximal responses by occupying 20-30 and 75-85% of the available 5-HT2A receptors, respectively. 5. The sensitivity to phenylephrine was not altered in hypertension. The mean pD2 values for phenylephrine were 7.14 +/- 0.05 (22) and 7.11 +/- 0.06 (22) on the WKY rat and SHR aorta, respectively. 6. These results show that there is a selective increase in sensitivity to 5-HT on the aorta in a rat model of genetic hypertension. There is also an increase in affinity for 5-HT at the 5-HT2A-receptors and a loss of 5-HT2A-receptor reserve for 5-HT responses on the aorta of SHRs.     

Susceptibility to neonatal streptozotocin-induced diabetes in spontaneously hypertensive rats

We studied the difference in the susceptibility to neonatal streptozotocin (STZ) diabetes between spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Two-day-old female SHR and WKY were injected intraperitoneally with 75.0 mg/kg of STZ or vehicle for control. Hyperglycemia developed in both strains at 4 days of age, but SHR were more hyperglycemic. Overt hyperglycemia developed in SHR with aging after a partial recovery from initial hyperglycemia at 10 days of age, whereas WKY did not develop significant hyperglycemia except shortly after STZ treatment. Percentage of insulin-positive B cells in total islet cells and pancreatic immunoreactive insulin (IRI) content were measured at 4 days, 10 days, 4 weeks, and 12 weeks of age. B cells per islet and pancreatic IRI content were significantly reduced in STZ-treated groups as compared with control in both SHR and WKY at 4 days of age, but later they increased significantly with aging in both strains. However, the reduction in pancreatic IRI content relative to control was significantly greater in SHR than in WKY from 4 days (-94.5 +/- 3.5%, -84.1 +/- 4.8%; p < 0.01) to 12 weeks (-97.1 +/- 2.1%, -28.0 +/- 2.5%; p < 0.05), and the reduction in B cells per islet was also greater in SHR at 4 weeks of age. These results indicated that the initial destruction of pancreatic B cells induced by STZ was greater, and the following regeneration was less in SHR than in WKY. The association of the susceptibility to neonatal STZ diabetes with the development of genetic hypertension in SHR remained to be elucidated.     

Milking procedure alters the electrolyte composition of spontaneously hypertensive and normotensive rat milk

A number of groups, including our own, have shown that the severity of hypertension expressed by the adult spontaneously hypertensive rat (SHR), which is primarily considered to be a genetic model of hypertension, can be reduced as a result of exposure to the behavioural and nutritional environment provided by a normotensive foster mother. It has been suggested that the hypertensive influence of the SHR dam may involve increased sodium delivery to the pups and there have been some reports of elevated sodium concentrations in the milk of SHR dams. However, these studies used either a long (> or =6 h) dam-pup separation period before collecting milk or repeated milking of the same dams, both of which have been shown to alter the trace element content of rat milk. Therefore, we have compared the electrolyte content of milk collected by these methods with milk derived from SHR and normotensive Wistar-Kyoto (WKY) dams separated from their litters for 2 h prior to a single-milking session. Long separation and repeated milking resulted in variable effects on the electrolyte content of both SHR and WKY dams' milk, compared with milk collected after 2 h from dams which had not previously been milked. The most notable effects were the abolition of significant strain differences, observed following 2-h separation, for milk sodium (WKY 22.1+/-1.4 vs. SHR 27.5+/-2.1 mmol/liter, p < 0.05) and calcium (WKY 92.3+/-4.3 vs. SHR 69.4+/-2.9 mmol/liter, p < 0.05) when dams were separated for 6 h or were serially milked. These data suggest that the electrolyte content of SHR and WKY dams' milk can be altered by the collection procedure and it is recommended that dams be milked on only one occasion following a short separation period from their litter.     

Effects of hyperbaric oxygen on rat embryos

The aim of the study was to investigate the toxic effects of hyperbaric oxygen (HBO) on rat embryos. Two groups of Fischer pregnant rats were exposed to oxygen at pressures of 324 and 426 kPa for 90 min per day for 5 consecutive days (8-12 days of gestation). The third group was exposed to normobaric oxygen for 12 h on the eighth day of gestation. Two control groups were used; the first was comprised of intact and the second of sham-treated animals. The HBO treatment did not significantly affect maternal weight gain or reduce litter size, nor did it induce any embryonic abnormalities. However, the fetal body weight was reduced and the placental weight increased in the groups exposed to HBO at pressures of 324 and 426 kPa. When female fetuses which had been exposed to oxygen at 324 or 426 kPa were compared to the intact control group, a reduction in wet weights of 9.2 (p < 0.05) and 12.1% (p < 0.01), respectively, was noted. Male fetuses exposed to oxygen at 324 and 426 kPa displayed a reduced body weight of 11.7 (p < 0.01) and 16.6% (p < 0.01), respectively. Placental weight was increased by 18.9 (p < 0.01) and 23.6% (p < 0.01) in the groups exposed to oxygen at 324 and 426 kPa, respectively. These data suggest that HBO, either at 324 or 426 kPa, is not potent at inducing malformations and that the largest embryotoxic effects are upon fetal body weight and placental weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance to endotoxin shock in spontaneously hypertensive rats

Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS.     

Alterations in heart and kidney membrane phospholipids in hypertension as observed by 31P nuclear magnetic resonance

Abnormalities of phospholipids in hypertension have previously been described in human erythrocyte, platelet, and plasma lipoproteins. Since the heart and kidney are adversely affected by hypertension, we investigated possible alterations in their membrane phospholipids, which could play a role in the derangement of intracellular ion balance widely observed in hypertension. The phospholipid compositions of heart and kidney from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were determined by using 31P nuclear magnetic resonance (NMR) spectroscopy. Absolute contents of all phospholipids in hypertensive hearts and kidneys were significantly higher than in normotensive hearts and kidneys. Expressed as a fraction of total phospholipid, cardiolipin (CL) and phosphatidylethanolamine plasmalogen (PEp) were significantly increased in SHR hearts compared to WKY hearts (CL and PEp were 7.95+/-0.22% and 13.16+/-0.35% in SHR vs. 7.01+/-0.20% and 11.19+/-0.42% in WKY rats, P< or =0.05), but phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were significantly decreased in SHR (PE and PC were 22.46+/-0.37% and 44.81+/-0.43% in SHR vs. 24.02+/-0.44% and 46.01+/-0.50% in WKY rats, P< or =0.05). In the phospholipids extracted from rat kidneys, the percentage of PE was significantly higher for SHR than for WKY rats (20.37+/-0.60% vs. 18.43+/-0.37%, P< or =0.05), while PEp and phosphatidylserine (PS) were significantly lower for SHR (PEp and PS were 10.22+/-0.36% and 8.42+/-0.28% in SHRs vs. 11.29+/-0.36% and 9.71+/-0.40% in WKY rats, P< or =0.05). The above alterations in phospholipid composition might contribute to the higher oxygen consumption in the hypertensive heart and abnormal intracellular ion concentrations and ion transport in the heart and the kidney in hypertension.     

Human lactoferrin receptor activity in non-encapsulated Haemophilus influenzae

We recently reported that attenuation of vasoactive agent-induced calcium signal and cell contraction of mesangial cell by insulin-like growth factor 1 (IGF-1), observed in normal mesangial cells, is totally abolished in spontaneously hypertensive rat (SHR) mesangial cells. This phenomenon might be related to the well-known aberrant regulation of SHR glomerular hemodynamics. Since it has been reported that in vivo IGF-1 infusion increases renal plasma flow (RPF) and glomerular filtration rate (GFR), we examined whether the modulation of renal function by IGF-1 is altered in SHR. We performed in vivo renal clearance studies using eight-week-old SHR and control Wistar Kyoto rats (WKY) before and after IGF-1 (5 micrograms/kg) infusion into the left renal artery for 20 minutes. Mean arterial pressure was not affected by IGF-1 in both WKY and SHR. In WKY, IGF-1 increased GFR and RPF, and decreased renal vascular resistance (RVR). However, GFR, RPF, and RVR were not altered by IGF-1 in SHR, while systemic infusion of angiotensin II antagonist, CV-11974, increased GFR and RPF. The present data show that the modulation of renal hemodynamics by IGF-1 is absent in SHR. This might be related the pathophysiology of the development of hypertension.     

Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3

AIMS: To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS: Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out beta thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS: Fetal serum GH concentrations in group A (median 29 micrograms/l, range 11-92) were significantly higher (P < 0.01) than those of group B (median 16.7 micrograms/l, range 4.5-29). IGF-I in group A (median 20 micrograms/l, range 4.1-53.3) was significantly lower (P < 0.01) than in group B (median 75.2 micrograms/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 micrograms/l, range 580-1260) were significantly lower than those of group B (median 1920 micrograms/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P < 0.0001) and IGFBP-3 (P < 0.0001) and negatively with GH (P < 0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices CONCLUSIONS: The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.     

Liver microsomal membrane fluidity and microsomal desaturase activities in adult spontaneously hypertensive rats

OBJECTIVE: The purpose of the present study was to investigate liver microsomal membrane fluidity simultaneously with membrane fatty acid composition and desaturase activities in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: The membrane fluidity was determined, after electron spin resonance (ESR) measurement, in SHR compared with normotensive Wistar-Kyoto (WKY) rats, by calculating the order parameter S from ESR spectra of 5-nitroxide stearate and 10-nitroxide stearate, used as spin-labelled fatty acids. Desaturase activities were measured by incubating SHR and WKY rat liver microsomes with [14C]-radiolabeled fatty acids as substrates for desaturation reactions. The fatty acid composition of liver microsomal membranes was determined by gas-liquid chromatography. RESULTS: Whereas no significant difference between S of 5-nitroxide stearate was observed for SHR and WKY rats, S of 10-nitroxide stearate was significantly lower in SHR than it was in WKY rat microsomal membrane, indicating that the core microsomal membrane fluidity was higher in SHR. Significant differences between fatty acid compositions were observed for SHR and WKY rat microsomal membranes. Delta9 and n-6 delta6 microsomal desaturase activities were significantly lower in SHR. CONCLUSION: These results suggest that the higher liver core microsomal membrane fluidity observed in SHR might be dependent on the increased proportion of mono-unsaturated fatty acids. Such observed modifications and the alterations in delta9 and n-6 delta6 desaturase activities suggest that an impaired polyunsaturated fatty acid biosynthesis is related to changes in microsomal membrane fluidity in hypertension.     

DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney

OBJECTIVE: Fetal growth and development are closely related to normal placental growth and function. We performed a study to determine the effect of a 10-day period of fetal hypoxemia induced by umbilical-placental hypoperfusion on tissue deoxyribonucleic acid synthesis rates in the 0.84 to 0.91 of gestation ovine fetus and placenta. STUDY DESIGN: Daily fetal placental embolization was performed in four chronically catheterized sheep fetuses until fetal arterial oxygen content decreased by approximately 30% compared with preembolization values. Five control fetuses received vehicle only. On experimental day 10, the deoxyribonucleic acid synthesis rate was determined by injecting tritiated thymidine (1 mCi/kg) intravenously approximately 8 hours before the end of the study. RESULTS: Fetal arterial oxygen decreased from 3.2 +/- 0.1 (SEM) mmol/L preembolization to 2.2 +/- 0.2 mmol/L on day 10 (p < 0.001) and remained unchanged in controls. On day 10 deoxyribonucleic acid synthesis rates were significantly reduced in embolized fetuses compared with controls, by 38% in cotyledons (83.0 +/- 15.1 vs 133.7 +/- 9.9 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), 28% in the left ventricular wall (36.8 +/- 3.7 vs 51.0 +/- 4.7 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05), and 45% in the quadriceps muscle (15.4 +/- 4.0 vs 28.1 +/- 3.0 disintegrations/min/micrograms deoxyribonucleic acid, p < 0.05). Tritiated thymidine autoradiography demonstrated that cotyledonary deoxyribonucleic acid synthesis occurred exclusively in the fetal trophoblasts cells. CONCLUSION: We concluded that a reduction in cotyledonary, quadriceps muscle, and left ventricular myocardium deoxyribonucleic acid synthesis rates are the earliest adaptive mechanisms of fetal growth associated with development of umbilical-placental insufficiency. We speculate that alteration in the myocardial deoxyribonucleic acid synthesis rate could be a major contributing factor in the deterioration of fetal myocardial function associated with increased placental vascular resistance.     

The effect of chronic hypertension on skin blood flow

OBJECTIVE: To determine whether the cutaneous microvasculature of the spontaneously hypertensive rat (SHR) is affected by chronic hypertension. DESIGN: We used laser Doppler techniques to measure skin blood flow in 22 SHR and in 22 non-hypertensive Wistar-Kyoto (WKY) rats over a 1-year time span, beginning at age 3 months. Sites of measurement included the back, leg, and root of the tail, areas with a predominantly nutritive perfusion, and the plantar surface of the paw, which has a large contribution from large arterioles and venules. Flow was measured at basal skin temperature and at the maximally heat-stimulated condition of 44 degrees C. Systolic tail arterial blood pressures were measured concurrently. RESULTS: At baseline, systolic blood pressures were considerably higher in the SHR (190 +/- 4 mmHg) than they were in the WKY rats (138 +/- 2 mmHg). Skin blood flow values at the three nutritive sites were similar in the two species. However, at 44 degrees C, flow was significantly higher at the paw in the SHR (46.8 +/- 3.5 versus 34.3 +/- 2.2 ml/min per 100 g). We attribute this difference to the effect of high perfusion pressure on large arterioles. During the 1-year measurement period, there was no appreciable change in blood flow in the WKY rats. In contrast, the SHR showed a steady progressive decline in skin blood flow at all sites. The largest decline was at the paw with a rate of fall of about 2.4%/month. After 1 year, there was no difference between paw blood flow in the SHR (27.5 +/- 1.8 ml/min per 100 g) and in the WKY rats (27.6 +/- 1.9 ml/min per 100 g). CONCLUSIONS: Skin blood flow reserve falls in response to chronic hypertension. The rate of fall is greater at sites with significant arteriovenous perfusion that at nutritive sites.     

Full expression of the exaggerated salt appetite of the spontaneously hypertensive rat requires a prenatal factor

1. The spontaneously hypertensive rat (SHR) exhibits a lower bodyweight in utero and an exaggerated salt appetite post partum. To determine whether salt appetite is affected by the perinatal environment, we measured the salt appetite of embryo-cross-transferred SHR and Wistar Kyoto (WKY) rats at maturity. 2. One-cell embryos were collected from the oviducts of donor rats and transferred into the oviducts of recipients through the infundibulum. The salt appetite of the resultant female offspring for 0.10 and 0.15 mol/L saline was measured at 20-30 weeks of age. 3. Salt intake of SHR gestated in WKY rats was significantly lower than that of SHR gestated in SHR, while that of WKY rats gestated in SHR was higher than that of WKY rats gestated in WKY rats. 4. Therefore, some maternal factor plays a role in the development of the exaggerated salt appetite of the SHR. This factor is also able to affect the later salt appetite of WKY rat offspring born to SHR surrogates.     

The platysma myocutaneous flap. Indications and caveats

Arterial hypertension has been identified as a major secondary risk factor for diabetic retinopathy. However, the mechanisms by which hypertension worsens retinopathy are unknown. Inhibition of advanced glycation product formation prevents the development of experimental diabetic retinopathy in normotensive diabetic rats. In this study the effect of hypertension on the rate of diabetic retinopathy development and the formation of arteriolar thrombosis was evaluated. We also evaluated the effect of aminoguanidine, an inhibitor of advanced glycation and product formation on retinal pathology of diabetic hypertensive rats. After 26 weeks of diabetes, hypertension accelerated the development of retinopathy despite a lower mean blood glucose level than in the non-hypertensive group (diabetic spontaneous hypertensive rats (SHR) 16.00 +/- 6.83 mmol/l; diabetic normotensive Wistar Kyoto rats (WKY) 34.9 +/- 3.64 mmol/l; p < 0.0001). Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR diabetic: 91.9 +/- 7.5 acellular capillaries per mm2 of retinal area vs WKY diabetic: 53.7 +/- 8.5 acellular capillaries per mm2 of retinal area), and a 3.8-fold increase in the number of arteriolar microthromboses (SHR diabetic 23,504 +/- 5523 microns2 vs SHR non-diabetic 6228 +/- 2707 microns2). Aminoguanidine treatment of SHR diabetic rats reduced the number of acellular capillaries by 50%, and completely prevented both arteriolar deposition of PAS-positive material and abnormal microthrombus formation. These data suggest that hypertension-induced deposition of glycated proteins in the retinal vasculature plays a central role in the acceleration of diabetic retinopathy by hypertension.