Met 235 Thr polymorphism of angiotensinogen in Indonesians

PURPOSE: To report a previously undescribed cause of bilateral macular hole formation. METHOD: Case report. RESULTS: Septic emboli were noted at the center of the macula in both eyes of a 32-year-old man with acute bacterial endocarditis. Bilateral full-thickness macular holes later developed at the site of these retinal lesions. CONCLUSION: This case represents the first report of fundus lesions in septicemia resulting in full-thickness macular hole formation.     

Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes

The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension. We investigated whether this allele also confers increased susceptibility to nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). A group of 380 patients who had had IDDM for 15 to 20 years were genotyped at the angiotensinogen 235 locus. Included were 75 patients with normoalbuminuria (albumin excretion rate < 30 micrograms/min), two series of patients with microalbuminuria (n = 30 and n = 136), and two series with overt proteinuria (n = 41 and n = 98). Allele 235T frequency was higher among cases with microalbuminuria (0.41 in the two series combined) or overt proteinuria (0.40) than in the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi 2 = 1.2, P = NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fold risk of developing nephropathy relative to carriers of other genotypes, but this value was not significantly different from 1(95% CI = 0.8 to 3.5). The strength of the association did not improve after stratification by degree of glycemic control. With respect to the hypertension in these IDDM patients, no association with allele 235T was found. Allele 235T frequencies in normotensive and hypertensive individuals were 0.363 and 0.353, respectively, among normoalbuminuric IDDM individuals (chi 2 = 0.01, P = NS) and 0.411 and 0.414 among microalbuminuric IDDM subjects (chi 2 = 0.0, P = NS). We conclude that the angiotensinogen polymorphism M235T might influence susceptibility to nephropathy in insulin-dependent diabetes, but its effect, if any, is rather small and independent of hypertension.     

Angiotensin-converting enzyme gene polymorphism in essential hypertensive patients in Japanese population

Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic background was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggest that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.     

Angiotensin converting enzyme variability in hypertensive and normotensive rats

Recent data have revealed biological and genetic variability in normotensive Wistar-Kyoto rats, which are considered to be the most appropriate control strain for spontaneously hypertensive rats. To investigate the possibility that angiotensin converting enzyme activity could be affected by this variability, we measured plasma and tissue (lung, heart, renal cortex, renal medulla, and adrenal gland) angiotensin converting enzyme activity in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats from three commercial suppliers in France: Iffa-Credo, Janvier, and Charles River Laboratories. Angiotensin converting enzyme activity was measured in vitro with a fluorometric assay using carbobenzoxy-Phe-His-Leu as substrate. Angiotensin converting enzyme activity in both rat strains varied considerably from one supplier to another, and therefore, comparisons of spontaneously hypertensive rats and Wistar-Kyoto rats from the different suppliers produced conflicting results. For Wistar-Kyoto rats, angiotensin converting enzyme activity in the plasma, heart, kidney, and adrenal glands was highest in rats from Iffa-Credo and lowest in rats from Charles River. For spontaneously hypertensive rats, angiotensin converting enzyme activity in the plasma and tissues was highest in rats from Janvier, whereas no difference could be observed between rats from Iffa-Credo and Charles River. These data confirm the problem of how to interpret and compare studies that use spontaneously hypertensive and Wistar-Kyoto rat strains.     

Prognosis of occlusive cerbrovascular diseases in normotensive and hypertensive subjects

Comparison of the clinical features, especially prognosis, in cerebral infarction was made between nine normotensive subjects and 16 hypertensive patients with an 80% stenosis or occlusion of the intracranial or extracranial arteries. Our own criteria for evaluating hypertension were employed on the basis of the following items: a past history of hypertension, blood pressure levels on admission and during hospitalization, degree of retinopathy, and ECG changes. In 17 of 25 cases, brain circulation was measured by the intravenous RISA technique. Abnormalities of the EEG and reduction of cranial blood flow were greater, and an early prognosis for neurological deficits in the first two months after the onset of stroke was poorer in the hypertensive group than inthe normotensive group. These results are contradictory to the observations of others.     

Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats

Conventionally, the hamstring:quadriceps strength ratio is calculated by dividing the maximal knee flexor (hamstring) moment by the maximal knee extensor (quadriceps) moment measured at identical angular velocity and contraction mode. The agonist-antagonist strength relationship for knee extension and flexion may, however, be better described by the more functional ratios of eccentric hamstring to concentric quadriceps moments (extension), and concentric hamstring to eccentric quadriceps moments (flexion). We compared functional and conventional isokinetic hamstring: quadriceps strength ratios and examined their relation to knee joint angle and joint angular velocity. Peak and angle-specific (50 degrees, 40 degrees, and 30 degrees of knee flexion) moments were determined during maximal concentric and eccentric muscle contractions (10 degrees to 90 degrees of motion; 30 and 240 deg/sec). Across movement speeds and contraction modes the functional ratios for different moments varied between 0.3 and 1.0 (peak and 50 degrees), 0.4 and 1.1 (40 degrees), and 0.4 and 1.4 (30 degrees). In contrast, conventional hamstring:quadriceps ratios were 0.5 to 0.6 based on peak and 50 degrees moments, 0.6 to 0.7 based on 40 degrees moment, and 0.6 to 0.8 based on 30 degrees moment. The functional hamstring:quadriceps ratio for fast knee extension yielded a 1:1 relationship, which increased with extended knee joint position, indicating a significant capacity of the hamstring muscles to provide dynamic knee joint stability in these conditions. The evaluation of knee joint function by use of isokinetic dynamometry should comprise data on functional and conventional hamstring:quadriceps ratios as well as data on absolute muscle strength.     

Regulation of preprotachykinin-A mRNA in genetic hypertensive and normotensive rats

It is well-known that central administration of tachykinins (Tks) inhibit salt intake in rats. Recent studies have shown that conditions that arouse salt appetite, such as adrenalectomy and sodium depletion, induce a decrease in preprotachykinin-A (PPT-A) mRNA in discrete regions of the rat brain, suggesting that reduced levels of PPT-A mRNA in the brain may have a permissive role on the expression of salt appetite. It has also been shown that spontaneously hypertensive rats (SHR) show higher avidity for salty solutions than their normotensive control Wistar-Kyoto (WKY) rats. In this regard, the present study tested whether SHR and WKY rats differ in expression of the gene coding for PPT-A, the precursor for Tks peptides. Using semi-quantitative in situ hybridization histochemistry, we examined the level of PPT-A mRNA in discrete rat brain regions of SHR and WKY rats under no treatment, after 1 or 3 days of Na+ depletion. Levels of PPT-A mRNA were analysed in the olfactory tubercle (Tu), in the lateral olfactory tubercle (LOT), in the dorsal and ventral caudate putamen (d/v CPu), in the medial preoptic area (mPOA), in the bed nucleus of the stria terminalis (BNST), in the habenula (Hb) and in the postero-dorsal part of the amygdala (MePD). Semi-quantitative analysis of silver grains revealed a 27.5% lower expression of the PPT-A mRNA levels in SHR opposite to WKY rats under no treatment in v-CPu, mPOA, BNST and Hb. 1 day of Na+ depletion reduced PPT-A mRNA levels when opposite to Na+-repleted animals in Tu and mPOA in both SHR and WKY rats. On the other hand, when comparing SHR and WKY rats after 1 day of Na+ depletion, a 26% lower level of PPT-A mRNA was detected in Tu and d-CPu of SHR opposite to WKY rats whereas a 14% and an 18% lower level was detected in v-CPu and Hb, respectively. A lower expression of PPT-A mRNA in SHR compared to WKY rats was also found in BNST and MePD, although no statistical significance was detected in these two brain areas. In the last experiment, 3 days of Na+ depletion reduced PPT-A mRNA levels in mPOA while negligibly increased mRNA levels in d-CPu and v-CPu, in BNST, Hb and MePD, both in SHR and WKY rats. Conversely, when making comparisons between the two strains, a 35% lower level of PPT-A mRNA in SHR with respect to WKY rats was found after 3 days of Na+ depletion in d-CPu, v-CPu and mPOA. A lower gene expression, even though not statistically significant, was found in Tu, LOT, MePD. These findings show a consistent difference of PPT-A mRNA levels in discrete regions of the SHR brain opposite to WKY rats and confirm that 1 day of Na+ depletion reduces PPT-A mRNA in discrete brain regions. Since SHR are notoriously more salt-avid than WKY rats and Tks are potent inhibitors of sodium intake, the down-regulation of PPT-A mRNA may contribute to the higher natriophilia and, therefore, to the etiology of the hypertensive disease.     

Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats

BACKGROUND: The detrimental effects of high dietary salt intake may not only involve effects on blood pressure and organ hypertrophy but also lead to tissue fibrosis independently of these factors. METHODS AND RESULTS: The effect of a normal (1%) or high (8%) sodium chloride diet on myocardial and renal fibrosis was assessed by quantitative histomorphometry in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The effect of salt on transforming growth factor-beta1 (TGF-beta1) gene expression was assessed by Northern blot hybridization. A high-salt diet from 8 to 16 weeks of age resulted in increased blood pressure and left ventricular and renal hypertrophy in both WKYs and SHRs. Marked interstitial fibrosis was demonstrated in the left ventricle (LV), glomeruli, and renal tubules and in intramyocardial arteries and arterioles but not in the right ventricle. The collagen volume fraction increased significantly after high-salt diet in the LV, intramyocardial arteries and arterioles, glomeruli, and peritubular areas in both WKYs and SHRs. In the kidneys, glomerular and peritubular type IV collagen was also increased. There was overexpression of TGF-beta1 mRNA in the LV and kidneys in both rat strains after a high-salt diet (all P<0.001). CONCLUSIONS: High dietary salt led to widespread fibrosis and increased TGF-beta1 in the heart and kidney in normotensive and hypertensive rats. These results suggest a specific effect of dietary salt on fibrosis, possibly via TGF-beta1-dependent pathways, and further suggest that excessive salt intake may be an important direct pathogenic factor for cardiovascular disease.     

Diurnal blood pressure patterns in normotensive and hypertensive children and adolescents

As abnormalities in diurnal ambulatory blood pressure (BP) have been associated with hypertensive target organ damage in adults, we investigated the diurnal systolic BP (SBP) and diastolic BP (DBP) patterns of 54 normotensive children, age 13.4 +/- 3.0 years, and 45 untreated borderline and mildly hypertensive children, age 14.4 +/- 2.6 years. Subjects wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. BP was measured q 15 min from 08.00-21.00 h then q 30 min from 21.00-08.00 h. Nocturnal BP fall, the night-day ratio and cusum derived measures were calculated from time-weighted daytime and night-time SBP and DBP. The groups were compared using analysis of covariance with adjustment for age, race, gender and body mass index. The influence of age, gender and race on the diurnal BP profile was also examined. Nocturnal SBP fall was greater in hypertensive compared to normotensive subjects (17.1 +/- 6.7 vs 14.6 +/- 7.1 mm Hg; unadjusted mean +/- s.d., P = 0.022). Normotensive and hypertensive groups did not differ in nocturnal DBP fall or SBP or DBP night-day ratio. Race appeared to influence the diurnal BP pattern as black subjects had less nocturnal SBP fall (12.9 +/- 6.9 vs 17.1 +/- 6.5 mm Hg; P < 0.005) and a higher night-day SBP ratio (90.1 +/- 5.3 vs 86.7 +/- 4.6%; P < 0.005) than white subjects. In conclusion, hypertensive children and adolescents have a similar diurnal BP pattern as their normotensive counterparts, except that the entire BP profile is shifted upward with a greater absolute fall in SBP at night. Race also appears to influence the diurnal BP profile of normotensive and hypertensive children and adolescents.     

Polymorphism in apolipoprotein(a) kringle IV 37(Met/Thr): frequency in a London population and its association with coronary artery disease

BACKGROUND: A raised concentration of lipoprotein(a) [Lp(a)] in human plasma has been considered as a risk factor for coronary artery disease (CAD). Apolipoprotein(a) and plasminogen genes are exceptionally similar to a variable number of plasminogen-like kringle IV repeats in the apo(a) gene. Polymorphisms have been previously identified in the apolipoprotein(a) kringle IV 37. HYPOTHESIS: In order to determine the frequency of the apolipoprotein(a) kringle IV 37 Met66-->Thr polymorphism in a London-based population and to assess the relationship of this polymorphism with CAD in Caucasian patients, we genotyped two groups of people of different ethnic origin (Caucasian and Afro-Caribbean) for the mutation using standard polymerase chain reaction (PCR) techniques. METHODS: The first group consisted of 182 unrelated Caucasian patients (107 men and 75 women, mean age 59.7 +/- 10.2 years) recruited at St. George's Hospital. They were defined as patients with 0, 1 or > or = 2 vessel disease patients depending on the degree of stenosis in none, one, or several major epicardial arteries. The second group comprised 64 unrelated patients of Afro-Caribbean origin attending a hypertension clinic at St. George's Hospital. RESULTS: It was shown that the prevalence of the Met66-->Thr mutation is markedly higher in Caucasians than in Afro-Caribbeans and that this mutation is not associated with either Lp(a) levels or severity of CAD.     

Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans

Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.     

Reduced fetal exposure to aspirin using a novel controlled-release preparation in normotensive and hypertensive pregnancies

OBJECTIVES: To examine the fetal effects of a novel controlled-release, low dose aspirin preparation in normal and hypertensive pregnancies. DESIGN: Random double-blind study. Participants assigned to receive conventional formulation aspirin (75 mg), controlled-release low dose aspirin (75 mg), or a matching placebo. SETTING: National Maternity Hospital, Dublin. PARTICIPANTS: Eighteen women with an uncomplicated pregnancy and 18 women with preeclampsia. MAIN OUTCOME MEASURES: Urine was analysed for metabolites of thromboxane and prostacyclin by gas chromatography, mass spectrometry. Serum thromboxane B2 was determined in maternal and cord blood. RESULTS: Both aspirin preparations reduced maternal serum thromboxane B2 by 95% and induced similar reductions in the urinary 11-dehydro-thromboxane B2, a major metabolite of thromboxane A2 in vivo. In contrast, neither preparation altered urinary 2,3-dinor-6-keto PGF1alpha, the major metabolite of prostacyclin. Despite their similar effects in the mothers, the two aspirin preparations differed in their effects on the fetus. While both suppressed cord fetal thromboxane B2, this was significantly (P < 0.005) less for the controlled-release preparation (210+/-42 ng/ml for placebo vs 109+/-22 ng/ml for controlled-release aspirin and 44+/-9 ng/ml for regular oral aspirin). CONCLUSIONS: At equivalent maternal suppression of serum thromboxane B2, a controlled aspirin release preparation results in lower fetal exposure than regular oral aspirin.     

Monoamine responses to acute and chronic aerobic exercise in normotensive and hypertensive subjects

OBJECTIVES: The purpose of the present study was to compare the plasma and serum monoamine levels in sedentary, untrained normotensive and hypertensive men at rest with levels measured after an acute bout of exercise and to compare similar measurements following a 12-week aerobic training program. PLACE OF STUDY: The data obtained for this study was collected from a clinic for the prevention of heart disease and cardiac rehabilitation (FITCOR) and analyzed in the Federal University of S?o Paulo (EPM), Laboratory of Experimental Neurology. SUBJECTS: Two groups of untrained male subjects, i.e., normotensive (N = 16) and hypertensive (N = 19), were submitted to an acute bout of exercise to analyze the acute effect of exercise on the monoamine levels. To study the chronic effect of exercise (physical training program), some individuals of each group were arranged in two other groups; normotensive (N = 11) and hypertensive (N = 8). MEASUREMENT: Plasma catecholamines and serum serotonin levels were determined by high performance liquid chromatography coupled with electrochemical detection. RESULTS: A significant reduction in diastolic blood pressure at rest was observed in the hypertensive group after the physical training program (p < 0.05). Only the mean plasma noradrenaline concentration increased significantly post-exercise in all groups of individuals (acute effect of exercise--p < 0.01 for untrained normotensive and hypertensive; chronic effect of exercise--p < 0.001 for untrained and trained normotensive, p < 0.01 for untrained and trained hypertensive). CONCLUSION: These data show the beneficial effect of physical exercise in reducing the blood pressure in hypertensive patients, which does not seem to be related to changes in circulating monoamines.     

Inadequate management of blood pressure in a hypertensive population

BACKGROUND: Many patients with hypertension have inadequate control of their blood pressure. Improving the treatment of hypertension requires an understanding of the ways in which physicians manage this condition and a means of assessing the efficacy of this care. METHODS: We examined the care of 800 hypertensive men at five Department of Veterans Affairs sites in New England over a two-year period. Their mean (+/-SD) age was 65.5+/-9.1 years, and the average duration of hypertension was 12.6+/-5.3 years. We used recursive partitioning to assess the probability that antihypertensive therapy would be increased at a given clinic visit using several variables. We then used these predictions to define the intensity of treatment for each patient during the study period, and we examined the associations between the intensity of treatment and the degree of control of blood pressure. RESULTS: Approximately 40 percent of the patients had a blood pressure of > or =160/90 mm Hg despite an average of more than six hypertension-related visits per year. Increases in therapy occurred during 6.7 percent of visits. Characteristics associated with an increase in antihypertensive therapy included increased levels of both systolic and diastolic blood pressure at that visit (but not previous visits), a previous change in therapy, the presence of coronary artery disease, and a scheduled visit. Patients who had more intensive therapy had significantly (P<0.01) better control of blood pressure. During the two-year period, systolic blood pressure declined by 6.3 mm Hg among patients with the most intensive treatment, but increased by 4.8 mm Hg among the patients with the least intensive treatment. CONCLUSIONS: In a selected population of older men, blood pressure was poorly controlled in many. Those who received more intensive medical therapy had better control. Many physicians are not aggressive enough in their approach to hypertension.     

Mechanical properties of human saphenous veins from normotensive and hypertensive patients

The three-dimensional structure of a synthetic peptide corresponding to the putative transmembrane segment M3 (amino acid residues 277-301) of the alpha subunit of the nicotinic acetylcholine receptor from Torpedo californica has been studied by means of two-dimensional 1H-NMR spectroscopy in a chloroform/methanol (1:1) mixture containing 0.1 M LiClO4. Complete resonance assignment has been performed using double-quantum-filtered COSY (DQF-COSY), TOCSY and NOESY spectra. The spatial structure has been calculated using the Diana program on the basis of integrated intensities of NOESY spectra. HN-C(alpha)H and HC(alpha)-C(beta)H spin-spin coupling constants. Residues 279-297 of M3 form a right-handed helix (root mean square deviation is 0.032 nm for backbone atoms and 0.088 nm for all heavy atoms). The conformations of the 17 side chains have been unambiguously determined. The obtained structure is in accord with the photolabeling pattern of the membrane nicotinic acetylcholine receptor (nAChR) which suggests alpha-helical structure of M3 in the labeled portion [Blanton, M. P. & Cohen, J. B. (1994) Biochemistry 33, 2859-2872].     

Lung function among black and white children

Racial differences in ventilatory lung function were evaluated in a community study of 393 children (158 blacks, 235 whites). Mean forced vital capacity was 18 per cent larger in nonsmoking white males than in nonsmoking black males, and 11 per cent larger in nonsmoking white females than in nonsmoking black females. Similar differences were observed for the 1-sec forced expiratory volume and for the maximal expiratory flow at 50 per cent of the vital capacity. However, when adjusted for lung size (on the basis of forced vital capacity), 1-sec forced expiratory volume and maximal expiratory flow at 50 per cent of the forced vital capacity were larger in the black children compared to the white children. Lung function prediction equations based on race, sex, age, height and weight are presented for healthy nonsmoking children; these allow for an evaluation of normal lung function in both black and white children.     

An electrogenic sodium pump and baroreceptor function in normotensive and spontaneously hypertensive rats

Postexcitatory depression (PED) and adaptation were examined in slowly adapting aortic baroreceptors of normotensive rats (NTR) and spontaneously hypertensive rats (SHR); an aortic arch-aortic nerve preparation in vitro was used. PED was elicited either mechanically by employing single or double pressure steps, or electrically by antidromic stimulation of the aortic nerve. During PED the axon of the receptor was capable of conducting action potentials and the receptor itself could respond to increased pressures. The relationship between duration of PED and number of impulses preceding it was hyperbolic. In NTR's and SHR's PED was abolished by ouabain or solutions containing no potassium, neither of which affected the steady state pressure-volume relationship of the aorta. These interventions, which are known to block electrogenic pumps, also lowered the pressure threshold and increased the curvature of the steady state pressure-frequency curve. Furthermore, lithium, another agent that blocks electrogenic pumps, also abolished PED. Thus, PED is attributed mainly to an electrogenic sodium pump which operates normally in baroreceptors. We found that adaptation from peak transient to steady state frequency did not appear to be altered significantly when the pump was blocked. Blockage of the pump by ouabain is responsible for the baroreceptor reflex effects elicited by this drug. We conclude that resetting and reduced sensitivity in SHR baroreceptors are not attributed to significant differences in electrogenic pump activity.     

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.