Effects of moderate diabetes on cardiac performance in spontaneously hypertensive and Wistar-Kyoto rats

To assess the effects of imposition of moderate diabetes on in vivo cardiac performance in gradually proceeding hypertension, spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were treated with streptozotocin (40 mg/kg) or vehicle at 8 weeks of age. Four and 20 weeks later, with the rats under ether anesthesia, peak cardiac output and stroke volume were measured during volume loading and peak left ventricular developed pressure and maximum rate of rise of pressure (dP/dtmax) were determined during aortic occlusion. Additionally, passive pressure-volume relations were obtained during saline infusion in potassium-arrested hearts, and the chamber stiffness constant was derived from one exponential function. There was a mortality of 16.1% in the diabetic SHR only. While basal and stressed cardiac performance was unchanged despite the already decreased mean arterial pressure and left ventricular weight at 4 weeks, the diabetic SHR revealed significant decreases in peak cardiac pumping indexes, peak left ventricular developed pressure, and dP/dtmax, with unchanged resting cardiac function, at 20 weeks. Changes seen in the diabetic WKY were reduced left ventricular weight at 4 weeks and reduced peak left ventricular dP/dtmax at 20 weeks. The chamber stiffness was unaltered with strain or diabetes. These data show that imposition of even moderate diabetes substantially influences the stress-loaded in vivo cardiac performance in the SHR, whereas it produces only minor changes in the WKY.     

Selective effects of alpha-methyldopa on myocardial cell components independent of cell size in normotensive and genetically hypertensive rats

Alpha methyldopa has been shown to modify left ventricular mass and normalize mitochondria/myofibrils volume ratio in spontaneously hypertensive rats (SHR) when administered during the stage of developing cardiac hypertrophy (Tomanek et al., Cardiovas Res 23: 173, 1979). To evaluate the long-term effects of this antihypertensive agent, the drug was administered to SHR and normotensive (WKY) rats between the ages of 1 and 12 months. In another group of SHR and WKY, treatment was delayed until the age of 12 months and the animals were then treated for 3 months. Treatment with alpha-methyldopa had similar effects on systolic blood pressures in both SHR groups; group means (+/- SEM) were 151 +/- 1 in the long-term treatment group and 157 +/- 5 in the delayed treatment group compared to 178 +/- 4 and 176 +/- 3 for their respective controls. While left ventricular weight and cell size were significantly lower after early long-term treatment (compared to nontreated SHR), delayed treatment had no significant effect on these indices of left ventricular mass. Despite the effectiveness of early long-term treatment in modifying left ventricular mass, the relative volumes of mitochondria and myofibrils, as well as other cellular components (sarcoplasm), were not altered. In contrast, delayed treatment caused a significant increase (approximately twofold) in relative sarcoplasmic volume and a decrease in relative myofibrillar volume in both SHR and WKY. These findings indicate that shifts in the relative volumes of intracellular components after alpha-methyldopa are independent of cell size and blood pressure. Furthermore, the data suggest that the effects of alpha-methyldopa on the myocardial cell are dependent on or influenced by factors associated with the development or stabilization of hypertrophy and/or age.     

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

Summary Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p<0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg·kg^–1 twice daily) or acutely as a single dose of 20 mg·kg^–1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p<0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p<0.05) and mortality (p<0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.     

Influence of long-term antihypertensive therapy on cardiac function, coronary flow and myocardial oxygen consumption in spontaneously hypertensive rats

The relationships between cardiac performance, coronary flow, coronary vascular resistance at maximal vasodilatation and myocardial oxygen consumption were determined in isolated hearts from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY) and from SHR given metoprolol (beta 1-selective blocker) and felodipine (selective calcium antagonist) for 35 weeks. A working heart perfusion system was used. An oxygen electrode allowed continuous measurement of oxygen tension in the venous coronary effluent. Blood pressure was reduced close to normal levels in treated SHR. Treatment also caused a substantial reduction of left ventricular weight. In both treated and untreated SHR, maximal cardiac performance, expressed as peak stroke volume, was enhanced above that of WKY at high perfusion pressures, while performance at low perfusion pressures was clearly reduced in the former groups. At a given workload, myocardial oxygen consumption (mmol O2/min per g) was reduced in both groups of SHR. This suggests a physiological structural adaptation to an elevated cardiac load in hypertension, where more myofibrils contribute to produce a given amount of work and therefore less oxygen is consumed per unit muscle mass. Coronary flow was reduced at any given perfusion pressure and oxygen extraction was increased in untreated SHR versus WKY. By causing regression of hypertensive structural vascular changes, treatment markedly increased coronary flow and correspondingly decreased oxygen extraction. Thus, by enhancing the myocardial nutritional supply with antihypertensive treatment, the reduced cardiac function at low perfusion pressure in untreated SHR was almost normalized.     

Ventricular performance in spontaneously hypertensive rats (SHR) with reduced cardiac mass

Summary This study was designed to investigate the effect of 4 weeks of captopril treatment on cardiac mass and performance in spontaneously hypertensive rats (SHR). Left (LV) and right (RV) ventricular mass of SHR and normotensive WKY rats was reduced (p<0.01). Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) in the treated SHR and WKY were reduced; cardiac (CI) and stroke (SI) indices remained unaltered in SHR but increased in WKY. Ventricular performance (i.e., cardiac pumping ability), assessed by rapid blood infusion, did not differ between untreated SHR and WKY, and between treated and untreated WKY rats. However, the ventricular performance curves for the treated SHR shifted down and to the right from the untreated SHR (p<0.01). Moreover, when MAP of treated SHR (with regressed LV mass) was elevated to their pretreatment levels, cardiac performance curves shifted further rightward and downward. In contrast, the performance curves of treated WKY whose MAP was also elevated to the level of untreated WKY were no different from those of untreated WKY. These data demonstrate that captopril treatment (at doses used in this study) reduced MAP in SHR through decreased TPRI while decreasing biventricular mass. Furthermore, the cardiac-pumping ability of previously hypertrophied SHR hearts was reduced, suggesting that certain antihypertensive agents that diminish cardiac mass could produce impaired cardiac function when called upon to increase performance (e.g., when MAP is suddenly raised).     

Neither ventricles nor afterload relief influence the raised plasma atrial natriuretic factor induced by volume expansion in the spontaneously hypertensive rat.

STUDY OBJECTIVE--The aims were (1) to study the influence of afterload relief on the rise in atrial natriuretic factor (ANF) which occurs during acute volume expansion in the spontaneously hypertensive rat (SHR); (2) to assess the contribution of the atria and the ventricles to ANF release under these circumstances. DESIGN--In the first series of experiments, SHR were treated with captopril (150 mg.kg-1.d-1) orally for 10 d. Untreated SHR and Wistar-Kyoto (WKY) rats served as controls. Volume expansion, equivalent to 10% of the total blood volume, was performed three times with human plasma protein fraction at 15 min intervals on conscious animals. Some haemodynamic variables and plasma ANF were measured. Tissue ANF measurements were conducted on another series of treated and control SHR not submitted to volume expansion. In another series of experiments, conscious SHR and WKY rats were submitted to repetitive 30% volume expansion (three times at 15 min intervals). Non-expanded animals served as controls. At the end of the experiments, tissue ANF measurements were performed. EXPERIMENTAL MATERIAL--All experiments were conducted on 15 week old SHR and WKY rats. MEASUREMENTS AND MAIN RESULTS--Captopril treatment reduced systolic blood pressure and cardiac hypertrophy in SHR. During volume expansion, changes in left ventricular end diastolic pressure were greater in control SHR than in treated SHR or WKY rats. Central venous pressure was affected similarly by volume expansion in both SHR groups. Plasma ANF rises induced by volume expansion were equal in all groups. Captopril treatment had no effect on right or left auricular ANF content prior to volume expansion. Repetitive 30% expansion reduced both right and left auricular ANF concentrations to the same extent (approximately 300-1500 ng.mg-1 protein) in SHR and WKY groups. Ventricular ANF was not affected by volume expansion in SHR, whereas volume expanded WKY rats had higher right and left ventricular ANF concentrations than their non-expanded controls. CONCLUSIONS--(1) The increase in plasma ANF during volume expansion is not impaired in SHR with newly established hypertension; (2) captopril treatment decreases afterload and the changes in left ventricular end diastolic pressure during volume expansion in SHR, without affecting plasma ANF increases; (3) both the auricles, but not the ventricles, contribute to enhanced ANF secretion caused by acute volume expansion in SHR and WKY rats.     

Compensated function in hypertrophied ventricles of Wistar Kyoto and spontaneously hypertensive rats

STUDY OBJECTIVE--The aim of the study was to compare the compensatory nature of left ventricular hypertrophy in models of normal and increased peripheral resistance. DESIGN--Peak left ventricular performance was compared in normotensive Wistar Kyoto (WKY) rats, in a subset of this strain with biventricular hypertrophy associated with volume overload (WKY-CH), and in spontaneously hypertensive rats (SHR), all studied at one year of age (ie, long term hypertrophy). SUBJECTS--8 WKY-CH rats with biventricular hypertrophy were compared with 8 WKY (normal right and left ventricular weights). These groups were then compared with 9 SHR rats. All were maintained under identical conditions. MEASUREMENTS AND MAIN RESULTS--Left ventricular to body weight ratios (mg:g) were as follows: WKY-CH 2.78(SEM 0.09); SHR 2.90(0.09); WKY 2.10(0.09). Systolic blood pressures (mm Hg) were normal in WKY-CH [104(9)] and WKY [111(9)], but raised in SHR [163(8)]. Left ventricles from WKY and WKY-CH had normal histology and no fibre disorientation, fibrosis, or other morphological abnormalities. Peak cardiac index (ml.min-1.body weight-1) measured during rapid volume expansion with Tyrode's solution was higher in WKY-CH [427(33)] than in WKY [315(33)] and SHR [349(31)] (p less than 0.05). When peak stroke volume was expressed per mg left ventricular weight there were no significant differences between the groups. Peripheral resistance (mean arterial pressure divided by cardiac output) at peak cardiac output was higher in SHR [1.20(0.12)] than in either WKY-CH [0.57(0.08)] or WKY [0.74(0.08)]. CONCLUSIONS--These data show that both types of hypertrophy enhance peak left ventricular performance. In WKY-CH, which have normal peripheral resistance, the larger ventricle allows a higher peak cardiac index compared to WKY with no left ventricular hypertrophy. In SHR, the higher left ventricular mass is used to overcome an increased peripheral resistance and thereby provide a normal peak cardiac index.     

Atrial Natriuretic Factor Release During Volume Expansion in the Spontaneously Hypertensive Rat - Effect of Long-Term Hydralazine Treatment

We tested the ability of spontaneously hypertensive rats (SHR) to release atrial natriuretic factor (ANF) during acute volume loading and its relationship to right and left atrial pressures. The effect of decreasing cardiac afterload by hypotensive treatment was also investigated. Fourteen to 15-week-old SHR and Wistar-Kyoto (WKY) rats were treated with hydralazine (12 mg/kg.day p.o.) for a period of 4 weeks. Untreated rats served as controls. The systolic blood pressure (BP) of SHR decreased to normotensive levels and cardiac hypertrophy was also reduced. Isotonic, iso-oncotic volume expansion (VE) was performed 3 times as 10% increments and at 15-min intervals. Despite greater changes in left-ventricular end-diastolic pressures (LVEDP) and to a lesser extent in central venous pressure (CVP) in SHR controls, the increases in plasma ANF (N-terminal concentrations) induced by VE were of a similar magnitude in both SHR and WKY control rats. The LVEDP and ANF C-terminal elevations were of a lower magnitude in treated SHR. Auricular ANF concentrations, measured at the end of VE, were lower in the left and higher in the right atrium in SHR versus WKY. It is concluded that despite a lower distensibility of their left atrium, ANF release is not impaired in SHR upon a VE. This adequate ANF release is obtained through higher increases in atrial pressures.     

Metabolic, hemodynamic, and cardiac effects of captopril in young, spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) demonstrate elevated blood pressure, cardiac hypertrophy, glucose intolerance, and insulin resistance compared with age-matched Wistar-Kyoto rats (WKY). We investigated concurrent effects of captopril on blood pressure, cardiac mass, myocardial enzyme activities, glucose tolerance, and insulin action in young male SHR. At 10 weeks of age, SHR were randomized into two groups, one receiving distilled water, the other a captopril solution (50 mg/kg body weight/day). We also examined age-matched WKY receiving distilled water. Blood pressure was measured by tail-cuff during the 4-week treatment period and oral glucose tolerance was tested at the end of treatment. Hearts were weighed and ventricular tissue was assayed for activities of 3-hydroxyacyl-CoA dehydrogenase, citrate synthase, and hexokinase. Growth rates were similar between captopril-treated and control SHR, but less than those of WKY. Captopril reduced blood pressure (134 +/- 8 v 177 +/- 8 mm Hg, P < .05) and left ventricular mass (-18%, P < .05) in SHR. Cardiac enzyme activities also changed with captopril treatment, reflecting an increased capacity for beta-oxidation of fatty acids and reduced potential for glucose phosphorylation in the left ventricle of SHR. Serum concentrations of glucose, insulin, and free fatty acids after a brief fast and in response to oral glucose were not different after captopril treatment, suggesting no improvement in insulin action or glucose tolerance. In summary, treatment of young male SHR with captopril reduces blood pressure and cardiac mass, and promotes a small but significant increase in cardiac capacity for oxidation of fatty acids and reduction of glucose phosphorylation. In contrast, metabolic effects of captopril on oral glucose tolerance and insulin action were not evident.     

Myocardial infarction in rats: effects of metabolic and pharmacologic interventions

Summary Myocardial infarction was induced in rats by ligation of the descending branch of the left coronary artery. The time course of changes in heart function was recorded within the first nine days. There was a progressive decline in LVSP, in LV dP/dt_max and in the pressure-rate-product. LVEDP was elevated. Cardiac output and stroke volume index were depressed after two days. The ATP content in the nonischemic region was lower than control, but recovered spontaneously toward the normal value within the first four days. Three metabolic and pharmacologic interventions known to affect cardiac adenine nucleotide metabolism were applied. Continuous i.v. administration of ribose which stimulates further adenine nuclcotide biosynthesis attenuated the fall and promoted the restoration of ATP in the nonischemic myocardium within four days after coronary artery ligation. The elevation of LVEDP was attenuated with ribose after two and four days. The calcium antagonist gallopamil administered as i.v. infusion for two days led to a further reduction of all parameters of left heart function, but did not influence the increase in adenine nucleotide and protein synthesis that occurred in the nonischemic heart. Coenzyme Q₁₀ had only slight effects on LVSP, LVEDP, and LV dP/dt_max, but attenuated significantly the fall in cardiac output and stroke volume index after two days following coronary artery ligation. Thus, all interventions affected differently the infarct-induced changes in heart and circulatory function. An improvement was observed with ribose and with coenzyme Q₁₀.     

Cardiovascular mass and ventricular function after celiprolol in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: The effects of a new beta 1 adrenergic receptor blocking agent with beta 2 receptor agonistic properties on cardiovascular mass, left ventricular function, and aortic distensibility were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. METHODS: 20 male SHR and 20 male WKY rats (10 treated and 10 untreated) aged 22 weeks were studied after three weeks of treatment. Cardiovascular mass was measured and left ventricular function was assessed using electromagnetic flowmetry while rapidly infusing whole blood at pharmacologically reduced mean arterial pressure and at pretreatment arterial pressure levels. Aortic distensibility was assessed by obtaining pressure-volume relationships in isolated aortic segments. RESULTS: Mean arterial pressure was reduced without changing cardiac output in SHR (p less than 0.01); it remained unchanged in WKY despite reduced cardiac output. Most noteworthy, and like no other agent studied to date, celiprolol significantly reduced both left and right ventricular as well as aortic mass in both WKY and SHR. Despite these similar mass reductions, celiprolol improved left ventricular function (p less than 0.01) and aortic distensibility (p less than 0.05) only in the SHR, a function maintained even when mean arterial pressure was increased abruptly to pretreatment levels. CONCLUSIONS: Unlike other beta receptor blockers (or any other agent studied in the SHR), celiprolol was effective in reducing mass of right and left ventricles and of aorta; decreasing mean arterial pressure through a fall in total peripheral resistance; and improving left ventricular function and aortic distensibility in the SHR. In contrast, while these structural changes were also produced in WKY, they were not associated with similar functional responses. These findings provide further support for the thesis of a structural and haemodynamic dissociation in antihypertensive therapy.     

Alterations in the Electrocardiogram of Spontaneously Hypertensive Rats by Chronic Antihypertensive Therapy With Captopril

To determine whether the electrocardiogram (ECG) could detect a reduction in ventricular mass with chronic antihypertensive therapy, ECGs were obtained in two year old female normotensive (NR) and spontaneously hypertensive rats (SHR) following nine months of treatment with captopril or water. The ECG of untreated SHR was considerably different than that of age- and sex-matched NR. The notable differences were the increased voltage, left axis deviation, a delay in the intrinsicoid deflection, and the increased frequency of left atrial abnormalities. Chronic captopril therapy produced a substantial reduction in left ventricular mass in the SHR (NR, 0.63±0.01; SHR, 1.08±0.03; captopril SHR, 0.80±0.04g). The ECG reflected this regression of left ventricular hypertrophy since the voltage and axis of the treated SHR were no longer different than those of NR. Thus, the ECG may be effective in evaluating the regression of cardiac hypertrophy in response to chronic therapy in experimental hypertension.     

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression

Summary The effect of myocardial depression on the circulatory response to acute normovolemic hemodilution (hematocrit 23%) with hetastarch was evaluated in 28 anesthetized Sprague-Dawley rats. Cardiac output was recorded using an electromagnetic flow probe. Mild, moderate, and severe myocardial depression were achieved by infusing disopyramide 50, 75, and 85 mg/kg. This resulted in a dose-dependent decrease in cardiac output (r=–0.73, p<0.05) and mean arterial pressure (r=–0.65, p<0.05), and an increase in left ventricular end-diastolic pressure (r=0.77, p<0.05) and total peripheral resistance (r=0.46, p<0.05). Following hemodilution, cardiac output and mean arterial pressure were significantly lower and total peripheral resistance significantly higher in animals with myocardial depression compared with saline anemic controls. These differences were dose-dependent for cardiac output (r=–0.83, p<0.05), mean arterial pressure (r=–0.68, p<0.05), and total peripheral resistance (r=0.51, p<0.05). Although control animals were able to significantly increase their cardiac output and stroke volume after hemodilution compared with baseline, animals with severe myocardial depression were unable to do so. This resulted in marked hypotension after hemodilution in controls compared with severely depressed animals. The results suggest a diminished ability of the pharmacologically depressed heart to tolerate acute normovolemic hemodilution.     

Effect of Long-Term Treatment with Diltiazem on Atrial Natriuretic Peptides in Spontaneously Hypertensive Rats

ABSTRACT

The present study was designed to examine the possible effect of long-term treatment with diltiazem on plasma and atrial concentrations of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR). Diltiazem treatment reduced blood pressure and ventricular weight in SHR. Plasma ANP concentration in untreated SHR was higher than Wistar-Kyoto rats (WKY). Diltiazem treatment decreased plasma ANP concentration in SHR near to the level of WKY; moreover, plasma ANP concentration was correlated with blood pressure and ventricular weight in treated and untreated SHR. Left atrial ANP concentration in untreated SHR was lower than WKY. Diltiazem treatment increased left atrial ANP concentration in SHR, but this effect was not noted in WKY. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that the prevention of an increase in plasma ANP by diltiazem treatment may be, in part, attributed to the improvement of cardiac overload induced by reductions in blood pressure and cardiac hypertrophy.     

Sympathetic nerves modify mitochondrial and capillary growth in normotensive and hypertensive rats

We tested the hypothesis that sympathetic nerves influence cardiocyte organelle volumes and capillarity in spontaneously hypertensive rats (SHR) with long-standing hypertension and left ventricular hypertrophy. SHR and their normotensive, Wistar Kyoto (WKY), controls were treated with 6-hydroxydopamine from birth to prevent the establishment of the sympathetic nervous system. To determine whether beta adrenergic receptors were the major pathway of sympathetic influence, another group of SHR and WKY were chronically treated from weaning with the beta 1 adrenergic antagonist, metoprolol. In SHR sympathectomy failed to alter, while metoprolol attenuated, hypertension. Stereological analyses of perfuse-fixed hearts showed that in both SHR and WKY mitochondria/myofibrils volume ratio was increased by long-term sympathectomy, mainly by limiting mitochondrial volume density, even though this intervention failed to alter left ventricular mass. In contrast, long-term beta 1 blockade attenuated hypertrophy in SHR but had no effect on mitochondria/myofibrils volume ratio. Capillary numerical density was increased significantly in sympathectomized SHR and WKY. However, despite this increase, capillary volume density was similar in control and sympathectomized rats, since capillary diameter was less in the latter. Metoprolol-treated SHR showed a trend toward higher capillary numerical densities consistent with their attenuation of hypertrophy. These findings indicate that sympathetic nerves, either directly or indirectly, inhibit cardiocyte mitochondrial growth and capillary proliferation during both normal and pressure-overload induced cardiac enlargement.     

复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响

目的 研究复方降压片对高血压大鼠冠状动脉壁肥厚和储备力下降的影响。方法 4w大鼠设4组：分别为自发性高血压大鼠(SHR)组、SHR口服复方降压片组、SHR口服卡托普利组和正常血压大鼠(WKY)组，饲养12w。冠脉最大血流量用离体心脏灌注法测定。结果 复方降压片能显著降低SHR收缩压、冠状动脉横截面积，提高最大冠状动脉流量，与卡托普利相似。复方降压片能降低SHR的左心室重与体重比，但仍然显著高于WKY组和口服卡托普利组。结论 复方降压片能预防SHR冠状动脉壁肥厚、储备力下降，减轻左心室肥厚；冠状动脉血流储备力的损害程度和左心室肥厚程度不平行。     

Interaction between lifetime captopril treatment and NaCI-sensitive hypertension in spontaneously hypertensive rats and Wistar-Kyoto rats.

DESIGN: Previous studies that were based on daytime arterial pressure recordings indicate that lifetime treatment with captopril exacerbates the hypertensive response to a high NaCl diet in spontaneously hypertensive rats (SHR) but has no such effect in normotensive Wistar-Kyoto (WKY) rats. The present study used 24-h recording methods to examine the hypothesis that during the normal waking hours of rats (night-time) the hypertensive response to a high NaCl diet is exacerbated in SHR and induced in WKY rats treated with lifetime captopril. METHODS: SHR and WKY rats were (1) untreated, (2), lifetime captopril treated or (3) lifetime captopril treated but removed from the treatment 2 weeks prior to exposure to a high (8%) NaCl diet RESULTS: Compared to untreated SHR, in SHR that were continuously treated with captopril, the high NaCl diet caused a more rapid and greater rise in arterial pressure. Discontinuation of the captopril treatment did not significantly diminish this NaCl-sensitivity. In untreated WKY rats, the high NaCl diet did not alter mean arterial pressure, but in the lifetime captopril-treated WKY rats the high NaCl diet induced a rapid rise in arterial pressure. In WKY rats, discontinuation of the lifetime captopril treatment did not diminish this NaCl-induced rise in arterial pressure, even though baseline mean arterial pressure in this group is similar to that in untreated WKY rats. CONCLUSIONS: Lifetime captopril treatment accelerates the hypertensive response to a high NaCl diet in SHR, and it induces a similar response in WKY rats. In both strains, the lifetime captopril treatment causes a change in the response that is not dependent on concurrent administration of the drug. This finding further suggests that lifetime captopril treatment causes a long-term resetting of cardiovascular response mechanisms.     

Changes in cardiovascular mass, left ventricular pumping ability and aortic distensibility after calcium antagonists in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVES: To determine the effects of different dihydropyridine calcium antagonists on cardiovascular mass and function in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: The rats were treated daily for 3 weeks with nitrendipine (20 mg/kg), nifedipine (30 mg/kg), nisoldipine (6 mg/kg) or their vehicles. At the conclusion of that period left ventricular pumping ability and aortic distensibility were determined, and the aortic, cardiac and left and right ventricular masses. RESULTS: Each drug reduced arterial pressure in both rat strains; each decreased left ventricular mass in SHR but not in WKY rats. All three agents increased right ventricular mass in WKY rats; only nisoldipine did so in SHR. Each compound improved left ventricular pumping ability in WKY rats, maintaining function even when pressure was abruptly increased to pretreatment levels. In contrast, although all three calcium antagonists improved cardiac performance in SHR at the pharmacologically reduced pressures, pumping ability was not maintained when pressure was increased to pretreatment levels in nisoldipine-treated SHR. All three agents improved aortic distensibility in both strains, but only in SHR was reduced aortic mass demonstrated. CONCLUSIONS: These data not only continue to demonstrate a functional/structural dissociation associated with antihypertensive therapy, but also suggest subtle functional and structural effects that differ even within the same class of calcium antagonists.     

Cardiac performance in rats with renal hypertension.

To evaluate cardiac performance in renal hypertension more precisely we determined cardiac function curves for 12 normotensive rats and 11 other rats with two-kidney Goldblatt hypertension. The hypertensive group (BP = 134 +/- 8 mm Hg) showed significant cardiac hypertrophy (44 +/- 1% increased ratio of heart weight to body weight, P less than 0.01) and markedly increased left ventricular stroke work with a moderate but not significant increase in left ventricular end-diastolic pressure (LVEDP) (5.9 +/- 0.8 vs. 4.7 +/- 0.4 mm Hg). We evaluated cardiac function by recording left ventricular end-diastolic pressure, stroke volume (SV), and cardiac output (CO) (by electromagnetic flowmeter) during rapid alteration in venous return. Analysis of variations of stroke volume vs. left ventricular end-diastolic pressure showed that renal hypertension is accompanied by a significant decrease in ventricular performance [SV = 0.0190 + 0.0509 LVEDP - 0.0025 (LVEDP)2 + 0.0001 (LVEDP)3] compared to the normotensive group [SV = 0.0430 + 0.0644 LVEDP - 0.0040 (LVEDP)2 + 0.001 (LVEDP)3]. The alterations in stroke volume and cardiac output were associated with a lack of significant changes in the work performed at matched end-diastolic pressures. The data indicate that chronic renal hypertension is accompanied by a depression of cardiac reserve which is not revealed by measurements of cardiac output and left ventricular end-diastolic pressure at rest. This impairment in cardiac function might be related to either diminished cardiac contractility or reduced left ventricular compliance; the latter possibility is in accord with our finding of a 2-fold increase in the hydroxyproline content (P less than 0.001) and a significant decrease in the DNA concentration of ventricular tissue.