Role of receptor elements in baroceptor resetting.

Spontaneously hypertensive rats (SHR), 4 wk of age, were treated with antihypertensive agents for 40 wk. The treatment was withdrawn for 2 wk so that the animals experienced hypertension for about 1 wk. The aortic arch was then perfused and aortic nerve activity was recorded. The threshold pressure was 140 mmHg in these SHR. This threshold pressure was less than that observed in age-matched untreated SHR (160--180 mmHg) but greater than that observed in age-matched Kyoto-Wistar rats (80--120 mmHg), indicating partial baroceptor resetting. No significant changes were observed in the vascular wall in these SHR, and partial baroceptor resetting was completely reversed when short duration of hypertension was reversed. On the other hand, baroceptor resetting in untreated SHR was always accompanied by significant changes in vascular wall, and reversal of baroceptor resetting was contingent upon regression of vascular wall hypertrophy. Partial baroceptor resetting in absence of significant changes in vascular wall may be explained by adaptation of baroceptors to persistent high blood pressure.     

Is the humoral renal antihypertensive activity of the spontaneously hypertensive rat (SHR) reset to the high blood pressure?

The kidneys have a humoral antihypertensive system, located in the renal medulla and presumably antagonizing the pro-hypertensive renin-angiotensin system. Medullipin I and II and maybe platelet activating factor (PAF), seem to be the mediators of this system, known to be activated after reversal of renovascular hypertension or when the perfusion pressure to a normotensive kidney is suddenly elevated. The present study was undertaken to investigate whether this system is functioning also in the spontaneously hypertensive rat (SHR), and if it is then reset in proportion to the increased mean arterial pressure (MAP). Isolated kidneys from spontaneously hypertensive rats and from Wistar Kyoto rats (WKY) were cross-perfused in vivo from anaesthetized intact Wistar Kyoto rat 'donors'. After 30 min of perfusion at 100 mmHg the perfusion pressure to the isolated kidneys were, for 60 min, either kept unaltered at 100 mmHg or, for the Wistar Kyoto rat kidneys, increased to 150-200 mmHg and, for the spontaneously hypertensive rat kidneys, raised to 200 or 250 mmHg. The results show that the humoral antihypertensive system is present also in spontaneously hypertensive rat kidneys, but is here reset upwards to or even beyond the elevated MAP level. Furthermore, all mean arterial pressure reductions caused by high-pressure perfusion of Wistar Kyoto and spontaneously hypertensive rat kidneys were accompanied by reductions in heart rate (HR) in the 'donors', in agreement with previous observations after reversing renal hypertension and after i.v. medullipin I injection. In fact, in spontaneously hypertensive rat kidneys, the 'incretory' depressor mechanism appears to be more markedly reset upwards than is the 'excretory' depressor mechanism inherent in pressure diuresis with consequent salt-volume elimination. In conclusion spontaneously hypertensive rats, like Wistar Kyoto rats and Wistar rats, have a humoral antihypertensive system in the kidneys, but it is reset upwards even beyond the elevated mean arterial pressure level in spontaneously hypertensive rats. The combination of a depressor response and reduced heart rate in the 'donors' renders further evidence that the medullipins are the principal, though probably not the only, humoral antihypertensive factors released from the cross-circulated kidneys.     

Resetting of aortic baroreceptors with non-myelinated afferent fibers in spontaneously hypertensive rats

The phenomenon of resetting and the possible mechanisms responsible for it were investigated in aortic baroreceptors having unmyelinated axons. Recordings were obtained from 31 aortic baroreceptor C-fibers in 20 normotensive Wistar Kyoto rats (WKY) and 37 baroreceptor C-fibers in 11 spontaneously hypertensive rats (SHR). The recordings were obtained from the left aortic nerve of an in vitro aortic nerve-aortic arch preparation. The thresholds for activation of baroreceptor C-fibers were not different between SHR's and WKY's at 16 weeks of age (139±7 and 133±5 mmHg, respectively). However, the thresholds for activation in SHR at 36 weeks of age were considerably higher (163±4 mmHg) indicating resetting of the receptors in the older rats. The pressure-discharge curves were not different between SHR's and WKY's at 16 weeks of age and WKY's at 35 weeks of age, but were shifted to the right for SHR's at 36 weeks of age. The receptors showed greater responses to pulsatile pressures than to steady state pressures at the same mean level of pressure. We found that aortic C-fibers were not reset during the early established phase of hypertension in SHR's because of enhanced receptor strain sensitivity. This is likely to be of importance for tonic vasomotor control at this time. In later stages of hypertension and despite enhanced strain sensitivity the endings were reset to higher pressures probably due to an increased collagen content in the aortic wall.     

Early-onset increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in SHR versus WKY.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p < 0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.     

Inhibition of renal sympathetic nerve traffic from cardiac receptors in normotensive and spontaneously hypertensive rats

The reflex inhibition of the sympathetic outflow to the kidney was examined during volume load with horse plasma in 6 normotensive rats (NCR) and 6 spontaneously hypertensive rats (SHR). The rats were anesthetized with chloralose and urethane. The arterial baroreceptors were denervated. The renal nervous inhibition was mediated via the vagal nerves and was mainly due to activation of receptors in the left side of the heart. The average thresholds in mean left atrial pressure for renal nervous inhibition was 5.4 mmHg for NCR and 9.2 mmHg for SHR indicating a clear resetting of the reflex arch in the hypertensive animal: The reason is probably a decreased distensibility of the wall of the left atrium due to a chronic elevation of left atrial pressure. This resetting of the atrial receptors in the hypertensive animals is probably of importance to allow an adequate filling pressure of the hypertrophied left ventricle and might also be of importance for the reflex neural control of renal function in these animals.     

抗高血压因子对大鼠血管平滑肌钙内流的影响

实验观察了从原发性高血压病患者红细胞中提取的抗高血压因子(AHF)对自发性高血压大鼠(SHR)、肾性高血压大鼠(RHR)和正常血压的WKY大鼠和Wistar大鼠主动脉和肠系膜动咏平滑肌Ca~(2+)内流的影响。结果表明,SHR和RHR的肠系膜动脉Ca~(2+)内流显著高于主动脉;AHF可显著抑制SHR和RHR主动脉和肠系膜动脉Ca~(2+)内流,抑制作用呈剂量依赖性,且对肠系腆动脉Ca~(2+)内流抑制作用更明显;AHF也可抑制正常动物血管平滑肌Ca~(2+)内流。本工作提示,AHF的降压机制可能与其抑制血管平滑肌特别是小动脉血管平滑肌Ca~(2+)内流有关。     

Ventricular morphology and pumping ability of exercised spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) and two strains of normotensive Wistar rats were subjected to a 5 day/wk swimming program to determine whether the heart of the SHR could respond to an additional stimulus to cardiac growth. Swimming was tolerated well by all rats. Although body weight of the exercised groups was not significantly reduced, both the right and left ventricular weights of all exercised groups were increased. Left ventricular circumference and chamber volume were increased without a change in free wall thickness in all exercised groups. Ventricular performance was assessed by peak cardiac output and stroke volume attained during rapid intravenous volume loading, both before and after autonomic inhibition. After combined cholinergic and beta-adrenergic inhibition, all exercised rats had slower heart rates and higher peak stroke volume than respectively sedentary controls. Thus, exercised SHR had the same alterations in cardiac mass and performance as exercised normotensive rats. Despite the initial presence of left ventricular hypertrophy, the SHR responded appropriately to an additional stimulus for adaptive cardiac growth.     

Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats

The aim of the present study was to assess the influence of ageing on cardiac function and coronary flow in Wistar Kyoto normotensive rats (WKY, 16 and 78 weeks of age) and spontaneously hypertensive rats (SHR) of the same age. Cardiac function was determined on isolated hearts by means of an antegrade heart perfusion technique. Left atrial pressure and peak aortic pressure could be altered independently of each other. Recordings of cardiac output and coronary flow were then obtained at both normotensive and hypertensive levels of peak aortic pressures. Peak stroke volume (SV) was reduced with age in both WKY and SHR. Peak SV determined at normotensive pressure loads became diminished with age in WKY, while it at hypertensive pressure loads showed a small decline with age, since peak SV was low as early as 16 weeks of age. The age-dependent fall in cardiac performance was greater in SHR than in WKY, due to the enhanced peak SV in 16-week-old SHR at hypertensive pressure loads. Peak SV was markedly decreased at normotensive pressure levels in both 16- and 78-week-old SHR v. age-matched WKY. Coronary flow per unit tissue declined with age both in WKY and SHR. Coronary flow was also lower in SHR compared to age-matched WKY. With ageing this elevated performance was reduced down to the same level as in 78-week-old WKY. The age-related coronary flow reduction and the consistently reduced flow in SHR indicate a structural narrowing of the coronary vascular bed, particularly in SHR.     

Increased lysyl oxidase activity in aortas of hypertensive rats and effect of beta-aminopropionitrile.

Lysyl oxidase activity was measured in aortas of spontaneously hypertensive (SHR) and deoxycorticosterone acetate-salt (DOCA-salt) induced hypertensive rats. Lysyl oxidase, the enzyme which catalyzes the initial step in cross-linking of collagen and elastin, was significantly elevated in aortas of both models of hypertension. Aortic collagen synthesis was increased in both models and collagen was significantly elevated in aortas of DOCA-salt hypertensive rats. Administration of β-aminopropionitrile (BAPN), an inhibitor of lysyl oxidase, before the onset of DOCA-hypertension prevented the development of hypertension and reduced lysyl oxidase and collagen content to control values. These results suggest that lysyl oxidase is instrumental in determining levels of aortic collagen content and that inhibitors of collagen and elastin crosslinking may be effective antihypertensive agents.     

Cardiac function and morphology with aging in the spontaneously hypertensive rat.

To determine the effects of a chronic pressure load on cardiac function and morphology, spontaneously hypertensive rats (SHR) and two normotensive strains of Wistar rats (WKY and NWR) were studied under ether anesthesia at 13, 25, 52, and 90 wk of age. Although resting cardiac index of the SHR was comparable to that of WKY and NWR at all ages, the peak cardiac output and peak stroke volume per gram of left ventricle determined during a rapid intravenous infusion of Tyrode solution was markedly reduced in the SHR only at 90 wk of age. Autonomic inhibition did not alter the peak stroke volume attained, but reduced peak cardiac output at all ages in each of the strains. Absolute left ventricular dimensions in the SHR increased out of proportion to body growth, consistent with concentric hypertrophy. As peak pumping ability markedly declined from 52 to 90 wk of age in the SHR, the free wall of the left ventricle greatly thickened whereas the septum remained unchanged. At this time the right ventricle also hypertrophied. This disproportionate thickening of the walls of the left ventricle and the hypertrophy of the right ventricle were reflected in measurements of their fiber diameters. These alterations in ventricular architecture may contribute to the decrease in pumping ability observed in long-standing hypertension.     

Contractility,Muscle Mass and Agonist Sensitivity of Isolated Portal Veins from Normo- and Hypertensive Rats

Properties of the longitudinal smooth muscle of portal veins from normotensive Wistar rats, adult (NCR) and young (NCR_y); spontaneously hypertensive Okamoto rats, adult (SHR) and young (SHR_y); and adult Wistar rats with renal hypertension (RHR) were studied in vitro and histologically. Some aortic strips from SHR and SHR_y were compared with controls. In response to noradrenaline (NA) and acetylcholine (ACh) greater maximum force was developed by veins from all hypertensive groups than by those from control rats. Cross-sectional area of the longitudinal muscle of veins from SHR but not SHR nor RHR was greater than control. Maximum stress in response to agonists was greater in both SHR and RHR than NCR. ED_so-values for NA and ACh were lower in portal veins from SHR than NCR but not from RHR nor SHR_y compared to controls. Denervation did not abolish any of the differences between SHR and NCR. Aortic strips from SHR developed less maximum force to NA and ED₅₀ was greater than those from NCR. i.e. opposite to the findings in portal veins. Low levels of external Ca^2- reveal altered calcium handling in veins from SHR compared to controls. It is concluded that portal veins from hypertensive rats are functionally different from those of normotensive rats and differ in SHR compared to RHR. It is suggested that the altered functional properties of portal vein, but not of aorta, in several respects resemble those of arterial resistance vessels. The implications of these findings are discussed in terms of mechanisms of hypertension in these animal models.     

Distensibility of left atrium in normotensive and spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR) left atrial mechanoreceptors are reset. Thus, left atrial pressure must be almost twice as high in SHR as in normotensive rats to produce comparable degrees of receptor activation and reflex sympathetic inhibition. The present study was performed to investigate whether this resetting is due to a decreased atrial distensibility in SHR. Static load-length relationships were therefore investigated on isolated left atrial strips from 11 pairs of male SHR and Wistar Kyoto rats (WKR). After each experiment the strips were fixed at a passive tension of 4 mN and the average wall thickness was determined histologically. Furthermore, pressure-volume relationships were studied on non-beating, isolated left atria from SHR and WKR. Distensibility was here defined as % volume increase when LAP was increased from 2.5 to 12.5 mmHg either rapidly (0.5–1 s, “dynamic” distension) or slowly (3 min, “static” distension). Atrial wall thickness did not differ significantly in SHR and WKR. but the passive force (mN) per crossectional area exerted during elongation above 80% was greater (P<0.05) in SHR. Also the “dynamic”, but not the “static” volume distensibility was significantly lower in SHR (P<0.01). The decreased dynamic distensibility of SHR left atrial walls can at least partly explain the resetting of the atrial receptors activated during the rapid filling phase.     

Inhibition of renal sympathetic nerve traffic from cardiac receptors in normotensive and spontaneously hypertensive rats.

The reflex inhibition of the sympathetic outflow to the kidney was examined during volume load with horse plasma in 6 normotensive rats (NCR) and 6 spontaneously hypertensive rats (SRH). The rats were anesthetized with chloralose and urethane. The arterial baroreceptors were denervated. The renal nervous inhibition was mediated via the vagal nerves and was mainly due to activation of receptors in the left side of the heart. The average thresholds in mean left artrial pressure for renal nervous inhibition was 5.4 mmHg for NCR and 9.2 mmHg for SHR indicating a clear resetting of the reflex arch in the hypertensive animal: The reason is probably a decreased distensibility of the wall of the left atrium due to a chronic elevation of left atrial pressure. This resetting of the atrial receptors in the hypertensive animals is probably of importance to allow an adequate filling pressure of the hypertrophied left ventricle and might also be of importance for the reflex neural control of renal function in these animals.     

Regression of myocardial hypertrophy and influence of adrenergic system

Studies of regression of myocardial hypertrophy in spontaneously hypertensive rats (SHR) suggest that the adrenergic system may play an important role in the reversal of hypertrophy. The effect of propranolol on reversal of hypertrophy, however, is still controversial. This study describes the effect of propranolol, given alone or in combination with hydralazine in different ratios for 4 wk, on blood pressure (BP), ventricular weight, and myocardial catecholamine (MC) concentrations. The data show that a certain ratio of propranolol to hydralazine (750:30) leads to moderate BP control (196-156 mmHg) without increased MC (634 vs. 552 ng/g) and moderately reduced hypertrophy. Reduction of BP alone with increased MC (hydralazine alone) or reduction of MC without BP control (propranolol alone) failed to reduce hypertrophy. A significant correlation between both ventricular weight and heart rate with MC (r = 0.6) was obtained by multiple regression analysis. This study suggests that adrenergic factors seem to play an important role in modulating structural cardiac response to variations in arterial pressure.     

Depolarization pattern of ventricular epicardium in two-kidney one-clip hypertensive rats

The present study is the first attempt to examine the effect of left ventricular hypertrophy (LVH) on the excitation pattern of the ventricular epicardium in experimental hypertensive rats. The left renal artery was clipped in Wistar rats (n = 8; 6-8 months old; weight, 174-295 g) to produce two-kidney one-clip (2K1C) hypertension. After 4 weeks, blood pressure was measured, and epicardial potential mapping was performed under sinus rhythm from 64 unipolar electrodes regularly distributed over the ventricular epicardium. Systolic blood pressure was approximately 40% higher in the rats with a clipped renal artery (162 +/- 14 mmHg, mean +/- s.d.) than in the normotensive rats (115 +/- 3 mmHg). LVH (approximately 23% increase in the ratio of the left ventricular weight to the body weight, P < 0.05) was observed in the 2K1C hypertensive rats. The depolarization pattern of the ventricular epicardium in the normotensive rats was similar to that in the rats with 2K1C hypertensive LVH. The duration of ventricular epicardial activation was shown to increase (approximately 35%, P < 0.05) in the hypertensive rats as compared to the normotensive animals. This study provides an explanation for alterations of the body surface potential distribution in hypertensive patients with LVH.     

Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy

The effects of renovascular hypertension and its reversal on the contractile performance of papillary muscles from rats has been examined. Hypertension of 10 wk duration caused a 48% increase in heart weight and significant prolongations of isometric time to peak tension (TPT), time to half relaxation, and time to peak shortening (TPS). A significant depression in the velocity of shortening was observed in the 10-wk group. However, muscles from hypertensive rats were still able to maintain normal levels of peak isometric developed tension and peak shortening; this may be due to the observed prolongation of TPT and TPS, respectively. In addition, calcium-activated actomyosin ATPase activity was depressed in hearts of hypertensive animals. Reversal of hypertension was studied at 20 wk after the onset of hypertension (10 wk of hypertension followed by 10 wk of normotension). Contractile and biochemical alterations observed in hypertensive animals were reversed in rats undergoing this regime. Thus reversal of a gradually applied pressure overload resulted in the regression of mechanical and biochemical abnormalities associated with the pressure overload myocardial hypertrophy.     

Comparison of the Somatosympathetic Reflex in Normotensive and Spontaneously Hypertensive Rats

Acute experiments under chloralose anaesthesia were performed in normotensive (Wistar and Wistar-Kyoto) and hypertensive (SHR) rats for recording of electrical discharge in the upper cervical sympathetic stem in response to stimulation of afferent fibers of the median nerve of the forelimb. These experiments showed that the evoked response was of the same shape in hypertensive rats as in normotensive rats. The latent period, duration of each discharge, and spectral characteristics of the somatosympathetic reflex were identical in animals of all the lines studied, though the amplitude of the reflex was greater in SHR rats than in normotensive animals. It is suggested that the organization of the somatosympathetic reflex is identical in hypertensive and normotensive rats. The reflex excitability of the sympathetic nervous system was increased in SHR rats.     

Performance of the hypertrophied left ventricle in spontaneously hypertensive rat. Effects of changes in preload and afterload.

Isolated hearts from adult spontaneously hypertensive rats (SHR; Okamoto 1969), with established hypertension, were investigated in an antegrade perfusion apparatus where preload and afterload could be varied independently. Frank-Starling curves were constructed at constant afterloads ranging from 50 mmHg to 150 mmHg. As earlier reported, the SHR hearts exhibited a rightward shift of their Frank-Startling relationships compared to those from the normotensive control hearts, though visible only at afterloads up to about 100 mmHg. At higher afterloads the SHR hearts performed significantly better then the NCR ones as their maximal stroke volume was significantly greater compared to that of controls. Thus, left ventricular hypertrophy obviously increases the work capacity of the heart, though at the cost of an altered Frank-Startling relation dependent on the reduced diastolic compliance. For such reasons the myocardial hypertrophy in established SHR hypertension must be considered a physiologic adaptation and not a degenerative phenomenon, though naturally degenerative processes may later become superimposed.     

Interaction between "mental stress" and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute "mental stress" could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During "rest" RSNA was higher in SHR than in WKY and it also increased more during "mental stress". The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44 +/- 0.06 vs. 0.78 +/- 0.08%/mmHg; p less than 0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6 +/- 0.2 vs. 2.9 +/- 0.4%/mmHg). If expressed (HR + 1 +/- 3%; p less than 0.025 vs. SHR and RSNA + 11% +/- 10, p less than 0.01 vs. SHR). These results) (0.10 +/- 0.02 vs. 0.06 +/- 0.01 microV/mmHg; p less than 0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

OBJECTIVE:

To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.

INTRODUCTION:

High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system.

METHODS:

Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg^-1) (SHR-Salt-S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves.

RESULTS:

The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar  =  109±2; SHR  =  118±2; SHR-Salt  =  117±2; SHR-Salt-S  =  116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar  =  2.90±0.06; SHR  =  3.44±0.07; SHR-Salt  =  3.68±0.07; SHR-Salt-S  =  3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar  =  -3698±92; SHR  =  -3729±125; SHR-Salt  =  -3342±80; SHR-Salt-S  =  -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar  =  1.40±0.04; SHR  =  1.60±0.05; SHR-Salt  =  1.67±0.12; SHR-Salt-S  =  1.45±0.03 mmHg/ml; P<0.05).

CONCLUSION:

Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.