alpha1-Adrenoceptor subtypes mediating the contraction of arteries in spontaneously hypertensive rats

1. This study was undertaken to determine which alpha1-adrenoceptor (AR) subtypes were involved in the activation of the femoral artery and the aorta by norepinephrine (NE) in spontaneously hypertensive rats (SHR). 2. Negative log EC50 values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Wistar-Kyoto (WKY) rats. 3. Contractile responses of the SHR aortas to NE were similar to those of the normotensive tissues. 4. Schild plot data for alpha1-AR antagonists indicated that alpha1-AR in the aorta were predominantly alpha1H subtype. In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were alpha1H (or alpha1C) and alpha1L subtypes. 5. The alpha1-AR subtype in the aorta was essentially identical to the alpha1H subtype in the femoral artery. alpha1-AR subtypes mediating contraction in the SHR blood vessels were identical to those in the WKY tissues.     

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.     

Membrane potential of mesenteric artery from carvedilol-treated spontaneously hypertensive rats

The effect of current, its magnitude and penetration enhancers (propylene glycol/oleic acid) on the transdermal flux of AZT (Zidovudine) across hairless mouse skin was studied and the results were compared. The in vitro iontophoretic flux from AZT solution increased to about 5-40 fold that obtained by passive diffusion, depending on the magnitude of current density. When the donor side was karaya gum matrix, instead of solution, the flux enhancement effect by iontophoresis was much smaller. Incorporation of penetration enhancers into the matrix increased the passive flux 2-50 fold, depending on the amount of penetration enhancers in the matrix. These enhancers worked synergistically with iontophoresis in the transdermal transport: a much larger flux than that expected from a simple additive effect was observed. Electrical resistance data from our previous work is utilized to further discuss this synergistic effect.     

Functional assessment of alpha 1-adrenoceptor subtypes in porcine coronary artery

1. alpha 1-Adrenoceptors are known to play an important role in vasoconstriction in response to adrenergic stimulation. However, the functional importance of alpha 1-adrenoceptor subtypes at the epicardial coronary artery remains unclear. We examined alpha 1-adrenoceptor subtypes by comparing functional affinities for alpha-adrenoceptor antagonists on noradrenaline (NA)-induced vasoconstriction in porcine denuded right coronary arteries. 2. Noradrenaline induced a dose-dependent vasoconstriction in incubated vessel rings. Prazosin and phentolamine were potent and competitive antagonists for NA-induced contraction (pA2 10.27 and 9.03, respectively). In contrast, the selective alpha 2-adrenoceptor antagonist yohimbine had a low affinity (pA2 6.13). Two selective alpha 1A-adrenoceptor antagonists, WB 4101 and 5-methyl urapidil, were potent and competitive antagonists of alpha 1-adrenoceptor-induced contraction (pA2 10.67 and 8.90, respectively) and the selective alpha 1D-adrenoceptor antagonist BMY 7378 had a low affinity (pA2 6.06). Noradrenaline-induced contraction was insensitive to the alkylating effects of chlorethylclonidine. These observations indicate that the vasoconstriction is predominantly mediated by the alpha 1A-adrenoceptor subtype. This was also supported by a good correlation between pA2 values from the present study and reported binding affinities (pKi) of various alpha-adrenoceptor antagonists with cloned human alpha 1A-adrenoceptors (r = 0.98), but not for alpha 1B- or alpha 1D-adrenoceptor subtypes (r = 0.77 and 0.41, respectively). 3. Our results indicate that the alpha 1A-adrenoceptor is the main functional receptor subtype in porcine denuded coronary arteries.     

Renal nerve responses to somatic nerve activation in stroke-prone spontaneously hypertensive rats

Antidepressant-induced adverse sexual effects are becoming more frequently reported by patients who require pharmacotherapy. A MED-LINE search was conducted to generate articles reporting such events. We report here on the sexual side effects associated with tricyclics, monoamine oxidase inhibitors including moclobemide, selective serotonin reuptake inhibitors, bupropion, and on the newer antidepressants venlafaxine and nefazadone. We conclude that adverse sexual effects are an increasingly important side effect of antidepressant medications, and patients must be routinely asked about their occurrence.     

Inhibition of alpha1-adrenoceptor-mediated contractions in isolated tail arteries and aorta of the rat by alpha2-adrenoceptor agonists

The effects of alpha2-adrenoceptor agonists, clonidine, tizanidine and UK-14304 on alpha1-adrenoceptor-mediated contractile responses were studied in isolated tail arteries and thoracic aorta of the rat. When applied during sustained contractile responses to almost maximum concentration (10 microM) of phenylephrine, clonidine (0.3 microM to 100 microM) produced concentration-dependent relaxations in both tissues. The maximum relaxation was smaller in tail arteries than in thoracic aorta. Clonidine up to 100 microM failed to relax both tissues precontracted with KCl (60 microM) or U-46619 (1 microM), a thromboxane mimetic. The clonidine-induced relaxation in tail arteries, was reversed by alpha2-adrenoceptor antagonists, yohimbine and idazoxane. Effects of the alpha2-adrenoceptor antagonists were concentration-dependent (0.1 microM to 1 microM), but not in a competitive manner. On the other hand, the relaxation in thoracic aorta was not significantly antagonized by these alpha2-adrenoceptor antagonists. Tizanidine and UK-14304 also relaxed both tail arteries and thoracic aorta precontracted with phenylephrine. The characteristics of the relaxation and their antagonism by yohimbine in both arteries were similar to those induce by clonidine. In tail arteries, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, at a concentration that completely inhibited acetylcholine-induced relaxations did not significantly affect the relaxation induced by clonidine. In contrast, the relaxation of thoracic aorta in response to clonidine was partly reduced in the presence of NG-nitro-L-arginine. These results indicate that the alpha2-adrenoceptor agonists selectively inhibit the contractions induced by phenylephrine in both tissues. Regional differences in the modes of the inhibition by the alpha2-adrenoceptor agonists exist.     

Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril

BACKGROUND: Hypertension is associated with endothelial dysfunction characterized by decreased endothelium-dependent relaxations and increased endothelium-dependent contractions. Angiotensin converting enzyme inhibitors and thromboxane A2 receptor antagonists decreased the endothelium dysfunction in hypertensive animals. OBJECTIVE: To investigate the effects of prolonged treatment with losartan on endothelium-dependent and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR). MATERIAL AND METHODS: Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/kg losartan per day or with 60 mg/kg captopril per day administered via their drinking water. The systolic blood pressure was evaluated basally and during week 12. At the end of the treatment period, the vascular reactivity in aortic rings was studies. A group of rats treated with captopril was studies as a reference group. RESULTS: Losartan and captopril reduced the blood pressure significantly and comparably. Both drugs enhanced acetylcholine-induced relaxations and reduced the maximal contractile response to acetylcholine in the presence of NG-nitro-L arginine methyl ester (L-NAME). Contractile responses to phenylephrine, endothelin-l and U46619 were not affected by these treatments. Increased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast this contractile response was elevated in rats treated with captopril. CONCLUSIONS: Prolonged antihypertensive treatments with losartan and captopril decreased the endothelial dysfunction in aortic rings from SHR not only by enhancing NO-dependent relaxations but also by reducing the contractions in response to an endothelium-derived contracting factor. The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfunction in SHR and the relationships between this factor and angiotensin II.     

Platelet lipoxygenase in spontaneously hypertensive rats

We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.     

Systemic hemodynamic and microvascular responses in spontaneously hypertensive rats during Escherichia coli bacteremia

Renovascular hypertension profoundly alters skeletal muscle arteriolar responses to sepsis, yet systemic hemodynamics to sepsis are not affected by hypertension. In this study, we hypothesized that microvascular responses of skeletal muscle and systemic hemodynamics are changed during high- and low-cardiac-output Escherichia coli bacteremia in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). During high-cardiac-output bacteremia, blood pressure and heart rate increased in WKY, but blood pressure decreased in SHR. During low-cardiac-output bacteremia, blood pressure initially decreased in WKY, while in SHR, pressure dropped significantly and remained severely depressed. Heart rate increased by 50% in SHR, but only by 10-15% in WKY during low-cardiac-output bacteremia. Large A1 and A2 arterioles constricted in both WKY and SHR during both phases of bacteremia. Small A3 and A4 arterioles dilated in WKY during bacteremia, but this small arteriole dilation was blunted in SHR. However, nitroprusside, an endothelium-derived relaxing factor (EDRF)-independently acting vasodilator, caused maximal dilation of these small arterioles of SHR. We conclude that there are profound changes and differences in systemic hemodynamics during bacteremia between the normotensive and the genetically hypertensive groups, whereas despite a possibly decreased endothelium-dependent vasodilator responsiveness in small arterioles of SHR during bacteremia, overall blood flow changes in skeletal muscle were similar among the two groups.     

Renal vascular responses to angiotensin II in conscious spontaneously hypertensive and normotensive rats

It has been postulated that exaggerated renal sensitivity to angiotensin II may be involved in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR). The purpose of this study was to compare the renal vascular responses to short-term angiotensin II infusions (50 ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical blood flow was measured in conscious rats by using quantitative renal perfusion imaging by magnetic resonance, and blood pressure was measured by an indwelling carotid catheter attached to a digital blood pressure analyzer. Renal vascular responses to angiotensin II were similar in control SHRs and WKY rats. Pretreatment with captopril to block endogenous production of angiotensin II significantly augmented the renal vascular response to exogenous angiotensin II in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin II were significantly greater in captopril-pretreated SHRs than in WKY rats (cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/- 1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely blocked in both strains by pretreatment with the angiotensin II AT1-receptor antagonist losartan. Results from this study in conscious rats confirm previous findings in anesthetized rats that (a) the short-term pressor and renal vascular responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs compared with WKY rats when endogenous production of angiotensin II is inhibited by captopril pretreatment.     

Effects of glibenclamide and nicorandil in post-ischaemic contractile dysfunction of perfused hearts in normotensive and spontaneously hypertensive rats

OBJECTIVE: We have demonstrated previously that nicorandil, an ATP-sensitive potassium channel opener, improved post-ischaemic contractile dysfunction of perfused hearts in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats dose-dependently. This study aimed to characterize the effect of glibenclamide, an ATP-sensitive potassium channel blocker, and nicorandil in post-ischaemic contractile dysfunction of SHR and WKY rats. METHODS: The perfused hearts were subjected to 30 min of global ischaemia and then 30 min of reperfusion. Administration of 10 or 50 mumol/l glibenclamide or of a combination of glibenclamide and 300 mumol/l nicorandil was performed for 10 min before the ischaemia. The left ventricular developed pressure and end-diastolic pressure were measured. RESULTS: Postischaemic contractile function was better in WKY rats than it was in SHR. Neither glibenclamide nor a combination of glibenclamide and nicorandil influenced the postischaemic contractile function or increased the incidence of reperfusion arrhythmias. The recoveries of coronary flow and heart rate after reperfusion were poor and the incidence of reperfusion arrhythmias was low in SHR. CONCLUSIONS: These results suggest that nicorandil improves postischaemic contractile dysfunction via a mechanism involving ATP-sensitive potassium channel opening both in SHR and in WKY rats. The hypertensive hearts were more susceptible to cardiac reperfusion dysfunction, compared with normal hearts.     

Comparison of the effects of hypercholesterolaemia on relaxation responses in aortas of spontaneously hypertensive rats and Dahl salt-sensitive rats

1. We investigated the effects of hypercholesterolaemia on relaxation responses in thoracic aortas isolated from two different types of hypertensive rats; spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats (DSR). 2. All rats fed the high cholesterol diet for 8 weeks showed a significant increase in the serum cholesterol level. The high cholesterol diet did not change the blood pressure of SHR, but increased that of hypertensive DSR fed a high-salt diet. 3. In aortas of SHR, the high-cholesterol diet did not change the endothelium-dependent and -independent relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. 4. In aortas of hypertensive DSR, the high-cholesterol diet notably reduced the ACh-induced relaxations and slightly reduced SNP-induced relaxation. 5. These results suggest that hypercholesterolaemia causes greater impairment of endothelium-dependent relaxation in rat aorta with salt-induced hypertension than genetic hypertension.     

Cilazapril reverses endothelium-dependent vasodilator response to acetylcholine in mesenteric artery from spontaneously hypertensive rats

This study was designed to evaluate the effect of chronic treatment with cilazapril on vascular reactivity of aorta and mesenteric artery from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg), an angiotensin converting enzyme inhibitor, was injected intraperitoneally twice a day for 4 weeks. Results demonstrated that acetylcholine (ACh)-induced relaxation in aorta and mesenteric artery from SHR was significantly less than that from WKY, cilazapril-treated WKY, and SHR. The impairment of ACh-induced relaxation in SHR was significantly reversed after cilazapril treatment and there were no significant differences among WKY, cilazapril-treated WKY, and SHR. Meanwhile, both N omega-nitro-L-arginine (LNNA; 10(-4) mol/L) and methylene blue (MB; 10(-5) mol/L) completely blocked the vasodilator response to ACh in aorta but only partly inhibited in mesenteric artery from WKY, cilazapril-treated WKY, and SHR. These LNNA- and MB-resistant vasodilator responses to ACh in mesenteric artery were only slightly inhibited by TEA (10(-3) mol/L) but not by indomethacin (5 x 10(-6) mol/L). These findings suggest that there may be an unidentified endothelium-dependent relaxing factor(s) (EDRF), which exists in the endothelium and may participate in the modulation of blood pressure in SHR. Results further demonstrate that the antihypertensive effect of cilazapril may be partly mediated by the reversing function of endothelium to release EDRF and LNNA-resistant, unidentified relaxing factor(s).     

Effects of kappa, sigma, and phencyclidine receptors agonists in rat tail arteries of spontaneously hypertensive rats

This review covers some of the more recent developments in the understanding of the different glucosyltransferases (GTFs) secreted by oral streptococci, particularly those produced by Streptococcus salivarius--a species that has been intensively studied at the Institute of Dental Research in Sydney.     

Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta

Previous studies showed that alpha-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by alpha 1b- and alpha 1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha 1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 micrograms/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against G alpha q and G alpha o but not G alpha s and G alpha i precipitated specific alpha 1-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G alpha proteins was increased by activating membrane alpha 1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G alpha q and G alpha o, and this response was blocked by the alpha 1-AR antagonist prazosin. Characterization of the alpha 1-AR subtypes that couple to G proteins indicates that although aortic alpha 1a-, alpha 1b-, and alpha 1d-ARs were associated with G alpha q, alpha 1b-AR was also linked to G alpha o. These results suggest that alpha 1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive G(o) protein.     

Alpha-adrenergic reactivity of the microcirculation in conscious spontaneously hypertensive rats

The goal of this study was to determine the functional distribution of alpha 1- and alpha 2-adrenoceptors in the striated muscle microcirculation. Experiments were performed in intact conscious spontaneously hypertensive rats (SHR) that were provided with a dorsal microcirculatory chamber to allow microvascular diameter measurements. Administration of selective alpha 1- and alpha 2-agonists, phenylephrine and azepexole, respectively, induced different patterns of microvascular constriction. alpha 1-Adrenoceptor stimulation showed a preferential constriction of large arteries and venules. The entire arteriolar microvasculature was sensitive to alpha 2-adrenoceptor stimulation, whereas the venular vessels did not respond to azepexole. The selective alpha 1- and alpha 2-antagonists prazosin and yohimbine showed patterns of vasodilator activity comparable to those of the corresponding agonists. The specificity of the drug-induced effects was verified by comparing their effects with those of graded hemorrhage, a non-pharmacological method for blood pressure lowering. In the range of blood pressure decreases comparable to that obtained by alpha-adrenoceptor antagonists, graded hemorrhage did not influence microvascular diameters. These results show a differential functional distribution of alpha 1- and alpha 2-adrenoceptors along the microvascular tree in striated muscle of conscious SHR.     

Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats

1. Noradrenergic (NA) nerve fibre distribution was investigated in the epicardium and myocardium of the heart in stroke-prone spontaneously hypertensive rats (SHRSP) and was compared to that in normotensive Wistar-Kyoto (WKY) rats. Fluorescent NA nerve fibres in the left and right epicardium of both strains aged 10, 30, 60, 90 and 180 days, and in the myocardium of left and right ventricles and the ventricular septum of both strains aged 30, 90 and 180 days were examined by the glyoxylic acid method. The distribution densities of NA nerve fibres were measured by quantitative image analysis. 2. The distribution pattern of NA nerve fibres in the epicardium of both strains showed a constant meshwork pattern throughout the entire examination period. 3. In the myocardium, NA nerve fibres were distributed irregularly between myocytes of both strains in all ages examined. 4. The densities of NA nerve fibres in the epicardium of SHRSP were significantly higher (P < 0.01 and 0.05; Student's t-test, 6 d.f.) than those of WKY at all ages examined except left epicardium at 90 days of age. 5. The densities in the right myocardium in 30 and 90 day old SHRSP were significantly higher (P < 0.05; Student's t-test, 6 d.f.) than those of WKY. 6. NA hyperinnervation in the epicardium and the myocardium of SHRSP may be assumed to be caused by the hyperfunction of the stellate ganglia which innervate the heart and may give rise to hypertrophy of the heart in SHRSP by a trophic effect of NA nerve fibre.     

Hypercapnic cerebral blood flow in spontaneously hypertensive rats

OBJECTIVE: Hypercapnic cerebral vasodilation appears to be endothelium-dependent, as it involves nitric oxide and prostaglandins. Since chronic hypertension has been associated with impaired endothelial function, we designed a study to find out whether hypercapnic cerebral blood flow and its nitric oxide- and prostaglandin-sensitive component is reduced in spontaneously hypertensive rats (SHR) compared with normotensive controls. METHODS: Cerebral blood flow was measured in enflurane-anesthetized SHR (n=53), Wistar-Kyoto (WKY, n=20) and Sprague-Dawley (n=50) rats using the hydrogen clearance method. Cerebral blood flow was measured during eucapnia and hypercapnia; it was also assessed after administering either nonisoform-selective or isoform-selective neuronal nitric oxide synthase inhibitors and during inhibition of prostaglandin production. RESULTS: Hypercapnic cerebral blood flow did not differ among the strains. Nitric oxide synthase inhibition with intracortical N(G)-monomethyl-L-arginine reduced hypercapnic cerebral blood flow in SHR by 23+/-4% and in Sprague-Dawley rats by 23+/-7% without affecting eucapnic flow. Intraperitoneal administration of the inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduced eucapnic flow by 18+/-5% in SHR and 27+/-5% in WKY rats, and hypercapnic flow by 48+/-3 and by 51+/-6%, respectively. Indomethacin produced a similar decrease in hypercapnic flow in Sprague-Dawley rats and SHR (49+/-5 and 62+/-4%, respectively). CONCLUSION: Hypercapnic cerebral blood flow was not impaired in SHR. The contribution of nitric oxide- and prostaglandin-dependent vasodilation appeared to be intact Our results are consistent with the hypothesis that neuronal rather than endothelial production of nitric oxide may be responsible for maintaining hypercapnic cerebral vasodilation in SHR.     

Peripheral nerve vascular changes in spontaneously hypertensive rats

Circulation to the brain is affected by hypertension. Hypertension-dependent cerebrovascular changes were documented primarily in brain pial arteries, whereas no information is so far available concerning changes of peripheral nerve vascularization in hypertension. This study was designed to assess the occurrence of structural changes of interfascicular and intrafascicular arteries supplying peripheral nerves (the so called vasa nervorum) in spontaneously hypertensive rats (SHR). The investigation was performed in 8-month-old SHR, by using standard microanatomical techniques associated with quantitative image analysis. In SHR a significant increase of systolic pressure values accompanied by thickening of the arterial wall, narrowing of the lumen and increase of the wall-to-lumen ratio were observed in comparison with age-matched normotensive Wistar-Kyoto rats. Hypertension-related structural changes involved primarily interfascicular arteries and to a lesser extent intrafascicular arteries. These findings indicate that similarly as documented for cerebral arteries, the vascular supply to peripheral nerves is impaired in hypertension. Structural changes of interfascicular and intrafascicular arteries of SHR could lead to ischemia of peripheral nerves. Further work is in progress to evaluate the functional relevance of hypertensive changes to peripheral nerve vasculature.