Development Of Salt-induced Hypertension Research Articles

Effects of Benidipine Hydrochloride on Autonomic Nervous Activity in Hypertensive Patients with Highand Low-salt Diets

The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.

The Kidneys and Aldosterone/Mineralocorticoid Receptor System in Salt-Sensitive Hypertension

Strong evidence supports the ability of the aldosterone/mineralocorticoid receptor (MR) system to dominate long-term blood pressure control. It is also increasingly recognized as an important mediator of cardiovascular and renal diseases, particularly in the presence of excessive salt intake. In a subgroup of individuals with metabolic syndrome, adipocyte-derived aldosterone-releasing factors cause inappropriate secretion of aldosterone in the adrenal glands during salt loading, resulting in the development of salt-induced hypertension and cardiac and renal damage. On the other hand, emerging data reveal that aldosterone is not a sole regulator of MR activity. We have identified the signaling crosstalk between MR and small GTPase Rac1 as a novel pathway to facilitate MR signaling. Such a local control system for MR can also be relevant to the pathogenesis of salt-sensitive hypertension, and future studies will clarify the detailed mechanism for the intricate regulation of the aldosterone/MR cascade.

High Perfusion Pressure Accelerates Renal Injury in Salt-Sensitive Hypertension

Renal injury in the Dahl salt-sensitive rat mimics human salt-sensitive forms of hypertension that are particularly prevalent in black individuals, but the mechanisms that lead to the development of this injury are incompletely understood. We studied the impact of renal perfusion pressure (RPP) on the development of renal injury in this model. During the development of salt-induced hypertension over 2 wk, the RPP to the left kidney was maintained at control levels (125 +/- 2 mmHg) by continuous servocontrol inflation of an aortic balloon implanted between the renal arteries; during the same period, the RPP to the right kidney rose to 164 +/- 8 mmHg. After 2 wk of a 4% salt diet, DNA microarray and real-time PCR identified genes related to fibrosis and epithelial-to-mesenchymal transition in the kidneys exposed to hypertension. The increased RPP to the right kidney accounted for differences in renal injury between the two kidneys, measured by percentage of injured cortical and juxtamedullary glomeruli, quantified proteinaceous casts, number of ED-1-positive cells per glomerular tuft area, and interstitial fibrosis. Interlobular arteriolar injury was not increased in the kidney exposed to elevated pressure but was reduced in the control kidney. We conclude that elevations of RPP contribute significantly to the fibrosis and epithelial-to-mesenchymal transition found in the early phases of hypertension in the salt-sensitive rat.

Existence of Multiple Blood Pressure loci on Rat Chromosome 13 of the Dahl S Hypertensive Rat

The aim of the present study was to identify the regions within Chr 13 involved in the development of salt-induced hypertension. We had previously reported an effect on salt-sensitive blood pressure and proteinuria, in a chromosome substitution strain for Chr 13. Consomic rats (SS-13BN) were backcrossed to Dahl SS (SS) rats, and the offspring intercrossed, to generate a population of 23 overlapping congenic rats for Chr 13. Blood pressure salt-sensitivity was determined after 2 weeks of high salt diet (8% NaCl) together with microalbuminuria. We found four discrete regions, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from salt-induced hypertension, reducing blood pressure sensitivity by 22–32 mmHg. Among the 23 congenic strains, several broadly overlapped with each other. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen between these regions, obtaining the same decrease in blood pressure as with each one independently, suggesting that these three regions act through the same final common pathway to lower blood pressure, through an epistatic interaction. Protection from salt-induced hypertension was more robust in female than in male rats in some of the congenic strains, suggesting a gender interaction with some of the genes determining blood pressure salt-sensitivity. Support: HL54998-09

Dietary sodium and blood pressure.

The importance of dietary sodium chloride in the regulation of blood pressure has received much attention over the past few years. This area of research and knowledge has been controversial for several reasons. The major reason for controversy is that the science of the relationship is difficult to ascertain. Population science is limited by the narrow range of dietary sodium intake by most populations and individuals and the multiple confounders in those populations at the extremes of intake. Results from clinical trials have been difficult to interpret because of the difficulty in maintaining a given level of sodium intake over a period of time sufficient for study. Furthermore, basic science studies have been challenged by identifying appropriate models that mimic salt-sensitive hypertension in humans. Moreover, a lack of a well-funded proponent in industry complicates the research challenges. Guyton’s concept that the role of the kidney in handling sodium is key to the long-term regulation of blood pressure is now generally accepted.1 However, the exact role that dietary sodium plays in this relationship remains controversial. The relationship between renal handling of sodium and blood pressure is apparently influenced by a complex combination of factors including nutritional, other environmental, genetic, neurohormonal, and metabolic factors. The skepticism of many regarding the role of dietary sodium in blood pressure regulation and control has been tempered by the results of the DASH sodium study.2 Most acknowledge that this study reliably confirmed the benefit of dietary sodium restriction in blood pressure management. The study showed a dose-dependent impact of dietary sodium restriction on blood pressure in older hypertensive and nonhypertensive subjects. For many interested in this area of research, the questions have shifted as a result of the DASH sodium study. Rather than questioning whether dietary sodium is important, many investigators have turned their …

Role of the alpha1D-adrenergic receptor in the development of salt-induced hypertension.

In an attempt to elucidate whether there is a specific alpha1-adrenergic receptor (alpha1-AR) subtype involved in the genesis or maintenance of hypertension, the alpha1D-AR subtype was evaluated in a model of salt-induced hypertension. The alpha1D-AR-deficient (alpha1D-/-) and control (alpha1D+/+) mice (n=8 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intraarterial BP recording. The alpha1D-/- mice had a significantly (P=0.0004) attenuated increase in BP response in this protocol (baseline 94.6+/-2.8 versus end point 107.4+/-4.5 mm Hg) compared with that of their wild-type counterparts (alpha1D+/+), from a baseline 97.4+/-2.9 to an end point 139.4+/-4.5 mm Hg. Seven of 15 alpha1D+/+ mice died with edema, probably owing to renal failure, whereas 14 of 15 alpha1D-/- mice were maintained for 35 days. Body weight, renal remnant weight, and residual renal function were similar in the 2 groups, whereas the values of plasma catecholamines (epinephrine, norepinephrine, and dopamine) were higher in alpha1D+/+ than in the alpha1D-/- mice. These data suggest that alpha1D-AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective alpha1D-AR antagonism could have significant therapeutic potential in the treatment of hypertension.

A Mechanism of Oxygen Free Radical Production in the Dahl Hypertensive Rat

To determine if oxygen free radicals derived from xanthine oxidase are involved in the development of salt-induced hypertension. Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction and provide a mechanism for lesion formation. Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a low-salt, high-salt or high-salt + tungsten diet for 4 wk. In vivo production of superoxide (O2-) was detected by the reduction of a tetranitroblue tetrazolium (TNBT) dye in the rat mesentery, while plasma hydrogen peroxide (H2O2) production levels were determined using a modified electrochemical electrode technique. The tungsten diet lowered the blood pressure of Dahl-S rats compared to high-salt-treated Dahl-S rats, but had no effect on blood pressure in Dahl-R rats. Light absorption of formazan deposits revealed that tungsten-treated Dahl-S rats had reduced TNBT staining along the endothelium of arterioles and venules compared to hypertensive, high-salt-treated Dahl-S rats. In addition, tungsten-treated Dahl-S rats had a lower plasma H2O2 concentration compared to hypertensive, high-salt-treated Dahl-S rats. These findings indicate that xanthine oxidase-derived oxygen free radicals are involved in the pathogenesis of salt-induced hypertension.

Oxidative stress in the Dahl hypertensive rat.

Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction, resistance to blood flow, and organ damage. The aim of this study was to determine whether oxygen free radicals are involved in the development of salt-induced hypertension. Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a high salt (6.0% NaCl) or low salt (0.3% NaCl) diet for 4 weeks. The high salt diet caused the development of severe hypertension in Dahl-S animals and had no effect on blood pressure in Dahl-R animals. A tetranitroblue tetrazolium dye was used to detect superoxide radicals in microvessels of the mesentery. Light absorption measurements revealed enhanced staining along the endothelium of arterioles and venules in hypertensive Dahl-S animals, with significantly lower values in normotensive animals. In addition, a Clark electrochemical electrode was used to measure hydrogen peroxide levels in fresh plasma. Hypertensive Dahl-S animals had a higher plasma hydrogen peroxide concentration compared with their normotensive counterparts (2.81+/-0.43 versus 2.10+/-0.41 micromol/L), while no difference was detected between high- and low salt-treated Dahl-R animals (1.70+/-0.35 versus 1.56+/-0.51 micromol/L). The plasma hydrogen peroxide levels of all groups correlated with mean arterial pressure (r=.77). These findings demonstrate an enhanced production of oxygen free radicals in the microvasculature of hypertensive Dahl-S rats.

Effect of Insulin on Norepinephrine Overflow at Peripheral Sympathetic Nerve Endings in Young Spontaneously Hypertensive Rats

To determine how the effect of insulin is related to the development of salt-induced hypertension, and whether a hyporesponse to insulin exists in the peripheral sympathetic nerves of a hypertensive model rat, we measured norepinephrine overflow from the periarterial nerve of isolated mesenteric arteries exposed to insulin in spontaneously hypertensive rats (SHR) as well as Wistar-Kyoto rats (WKY) fed diets that were high and low in salt. Salt loading (diet containing 8% salt for 4 weeks) accelerated the development of hypertension in young, spontaneously hypertensive rats (SHR) (157 +/- 5 mm Hg v 198 +/- 4 mm Hg, P < .01) but did not affect the blood pressure of Wistar-Kyoto rats (WKY) (102 +/- 7 mm Hg v 104 +/- 6 mm Hg, P = NS). Basal norepinephrine overflow did not differ in the SHR and WKY rats, but the overflow of norepinephrine after periarterial electrical stimulation (8 Hz 1 min.) was significantly greater in SHR (0.806 +/- 0.079 ng/g) than in WKY (0.723 +/- 0.022 ng/g; P < .01). Although insulin reduced the norepinephrine overflow by periarterial nerve stimulation in both WKY and SHR, the decrease with insulin was significantly greater in the SHR than in WKY (-18.4% +/- 4.0% v -32.0% +/- 4.6%, P < .05). The inhibitory effect of insulin on norepinephrine overflow was reduced by salt loading in SHR (-8.8% +/- 4.0%, P < .05), but not in WKY (-32.5% +/- 4.7%, P = NS). Cocaine and ouabain completely blocked the effect of insulin in all four groups. In contrast to insulin, direct stimulation of Na(+)-K+ ATPase with a high-potassium buffer (12 mmol/L) reduced NE overflow to the same extent among the four groups. These findings show that SHR have a blunted response to the suppression by insulin of norepinephrine overflow. Salt loading reduced the insulin response at peripheral sympathetic nerves of young SHR, but did not affect that of age-matched WKY. Thus, hyporeactivity to insulin may play a role in the development of salt-induced hypertension in young SHR, possibly through a reduced suppression of norepinephrine overflow from sympathetic nerve endings.

Effects of vasopressin V1 and V2 receptor antagonists on the development of salt-induced hypertension in Dahl rats.

To determine whether the vasopressor and antidiuretic actions of arginine vasopressin (AVP) may participate in the development of salt-induced hypertension, we examined the long-term effects of AVP V1 and V2 receptor antagonists on blood pressure (BP) in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats. From age 7 weeks, DS and DR rats were fed a diet containing 8% NaCl, alone (control group); 8% NaCl and 1% OPC-21268 (V1 antagonist-treated group); or 8% NaCl and 0.05% OPC-31260 (V2 antagonist-treated group). The pressor response to AVP was significantly inhibited in DS rats treated with OPC-21268. Urinary volume and water intake were significantly increased by administration of OPC-31260; this increase was greater in DR rats than in DS rats. Indirect BP measurements obtained using tailcuff plethysmography showed that DS but not DR rats developed hypertension when fed high-salt diets. However, chronic treatment with either OPC-21268 or OPC-31260 did not alter the course of hypertension in DS rats, despite the effective blocking actions of these antagonists. This finding also was confirmed by direct BP measurements. Our results indicate that even if AVP plays a role in salt-induced hypertension peripheral blockade of either subtype of AVP receptors does not prevent the development of hypertension in DS rats.

Dietary sodium intake modulates vasodilation mediated by nitroprusside but not by methacholine in the human forearm.

Studies in animals suggest that nitric oxide production is increased under conditions of salt loading and that this increase protects against the development of salt-induced hypertension. To determine the effect of dietary sodium intake on nitric oxide-mediated vascular responses, we studied seven healthy male volunteers twice 4 weeks apart while they were receiving a diet containing 10 or 250 mmol Na+ per 24 hours. Methacholine (0.25 to 8 micrograms/min) and sodium nitroprusside (0.25 to 8 micrograms/min) were infused intra-arterially in incremental doses, and forearm blood flow was measured. The response of forearm blood flow to sodium nitroprusside was greater when subjects received a high sodium diet than when they received a low sodium diet (F = 7.11, P < .05); however, the response to methacholine was not altered by sodium intake (F = 0.57, P = NS). Plasma renin activity was significantly higher (3.99 versus 1.0 ng angiotensin I/mL per hour) when subjects received a low salt diet (P < .05). Systolic pressure, diastolic pressure, heart rate, and baseline forearm blood flow were not affected by sodium status. We conclude that under conditions of salt loading, vasodilation in response to sodium nitroprusside was enhanced, whereas the response to methacholine was not affected, suggesting a differential effect of sodium intake on endothelium-dependent and endothelium-independent responses after the administration of methacholine and sodium nitroprusside, respectively.

Antihypertensive Property and Renal Protection by Shichimotsu-koka-to Extract in Salt-induced Hypertension in Dahl Strain Rats

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Role of Centro-Renal Noradrenergic Systems in the Development of Salt-induced Hypertension

Role of Centro-Renal Noradrenergic Systems in the Development of Salt-induced Hypertension

Salt-induced plasticity in cardiopulmonary baroreceptor reflexes in salt-resistant hypertensive patients.

To investigate the effects of salt loading on cardiopulmonary and arterial baroreceptor reflexes, 34 hypertensive patients underwent two 4-day periods with different dietary sodium intakes (70 and 370 meq/day). The patients were classified as salt-sensitive or salt-resistant depending on whether the mean arterial pressure value obtained on day 4 of high salt intake did or did not increase by 8% or more. In 22 patients cardiopulmonary and carotid baroreceptor reflexes were assessed during each dietary period by measuring the reflex responses to the application of -10 mm Hg lower body negative pressure and of +60 mm Hg increase in neck tissue pressure. Salt-resistant patients (n = 16) retained less sodium than salt-sensitive patients (n = 6) and showed a reduction in plasma norepinephrine and forearm vascular resistance during high sodium intake, whereas the salt-sensitive patients did not. During low sodium diet, no significant differences could be detected in the reflex responses to cardiopulmonary and carotid baroreceptor unloading between the two groups. High salt diet, however, potentiated the gain of cardiopulmonary baroreceptor reflex, which was expressed as the increase in plasma norepinephrine or forearm vascular resistance per millimeter of mercury decrease in pulmonary capillary wedge pressure, only in the salt-resistant hypertensive patients. In addition, the atrial natriuretic factor response to changes in pulmonary capillary wedge pressure was significantly enhanced by high salt intake only in the salt-resistant hypertensive patients. The reflex responses to carotid baroreceptor unloading were unaffected by salt loading in either group. In the remaining 12 patients, the hemodynamic effects of graded lower body negative pressure (-5, -10, -15 mm Hg) and neck tissue positive pressure (+30, +45, +60 mm Hg) were tested for both diets. Again, high salt intake significantly potentiated the cardiopulmonary baroreceptor reflex gain, expressed as the slope of the linear correlation between the changes in forearm vascular resistance (mm Hg/ml/min/100 g) and pulmonary capillary wedge pressure (mm Hg), in salt-resistant (from 3.8 +/- 0.9 to 7.2 +/- 1.0, p less than 0.05) but not in salt-sensitive patients (from 4.2 +/- 0.9 to 3.2 +/- 0.6, NS). In conclusion, the present study demonstrates that high salt diet potentiates cardiopulmonary baroreceptor reflexes and enhances atrial natriuretic factor response in salt-resistant but not in salt-sensitive hypertensive patients. The salt-induced plasticity of cardiopulmonary baroreceptor reflexes may exert a protective effect against the development of salt-induced hypertension by augmenting the reflex vasodilatory response to volume expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

Sodium regulation in the affinity of renal alpha 2-adrenoceptors for epinephrine in Sabra salt-sensitive and salt-resistant rats.

Sodium ions markedly decreased in vitro renal alpha 2-adrenoceptor affinity for epinephrine in Sabra hypertensive (SBH) but not in normotensive (SBN) rats. Under these conditions, affinity of alpha 1-adrenoceptor for epinephrine was unchanged in SBH and SBN rats. If these data could be confirmed in vivo, the sodium ion, by acting as an inhibitor, could modify the effect of agonists on renal alpha 2-adrenoceptors in SBH rats. Conversely, the absence of sodium regulation in SBN rats might represent a genetically mediated change responsible for the resistance to the development of salt-induced hypertension.

Altered peripheral noradrenergic activity in intact and sinoaortic denervated Dahl rats

Development of salt-induced hypertension in Dahl salt-sensitive (S) rats is dependent on sympathetic overactivity which may be partially related to arterial baroreflex dysfunction and, therefore, is regionally selective. Our first experiment was designed to determine which regions have elevated sympathetic activity in Dahl S compared with Dahl salt-resistant (R) rats. Weanling (4-week-old) female Dahl R and S rats were fed low or high salt diets (0.13% and 8% NaCl) until 10 weeks of age. Norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the fractional decline of NE concentration was measured in various tissues. Dahl S rats with increases in both arterial pressure and left ventricular weight demonstrated increased NE turnover in the sinoatrial node, the atrial appendages, the cardiac ventricles, and the renal cortex. In all of these tissues except the cardiac ventricle, increases were associated with high salt intake. Our second experiment was designed to test if arterial baroreflex dysfunction could account for regional increases in sympathetic activity. Separate groups of Dahl R and S rats fed high salt were subjected to either sham surgery or sinoaortic baroreceptor denervation 1 week prior to turnover determinations. Sinoaortic baroreceptor denervation abolished differences in NE turnover between salt-fed Dahl R and S rats in the cardiac sinoatrial node and the atrial appendages, but not in the cardiac ventricles and the renal cortex. Sinoaortic baroreceptor denervation also abolished differences between salt-fed Dahl S and R rats in the spleen but not the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin-angiotensin and vasopressin in the development of salt-induced hypertension.

The purpose of this study was to assess the participation and interaction of the renin-angiotensin system and vasopressin in the early stages of the development of salt-induced hypertension. Subtotally nephrectomized rats, fed 1% saline, were treated over a 10-day period with either an antivasopressor V1 antagonist (by osmotic minipump) or an angiotensin converting enzyme inhibitor (either captopril or ramipril, given daily by oral gavage), or a combination of the two modes of treatment. Surprisingly, only ramipril (either alone or in combination with the V1 antagonist) could prevent the development of hypertension in these animals. Our data would not permit conclusion as to whether the different capacity of these agents to prevent salt-induced hypertension was due to a different degree of penetration into the central nervous system, or to some other property.

Calcium Channel Blockade with Verapamil: Effects on Blood Pressure, Renal, and Myocardial Adrenergic, Cholinergic, and Calcium Channel Receptors in Inbred Dahl Hypertension-Sensitive (S/JR) and Hypertension-Resistant (R/JR) Rats

Verapamil HCl was chronically administered to inbred Dahl S/JR and R/JR rats maintained on a diet containing 8.0% NaCl (w/w) and the effects on blood pressure (BP) and heart rate (HR) were investigated. Treatment over a 4-week period via implanted miniosmotic pumps attenuated but did not prevent the development of salt-induced hypertension (HT) in the S/JR rat. Elevated HR, possibly reflexive in origin, was observed in S/JR rats that received verapamil but not in similarly treated R/JR rats. Although verapamil retarded the development of HT in S/JR rats, BP rose to moderately hypertensive levels, and the ventricle/body weight ratio was elevated by the termination of the study. The effect of verapamil on the density and affinity of alpha 1-, alpha 2-, and beta-adrenergic, muscarinic cholinergic, and calcium channel receptors in renal and ventricular membranes was also assessed. The density of renal and ventricular alpha 1- and beta-adrenoceptors was not affected by chronic drug treatment. The density of renal alpha 2- and beta-adrenoceptors was greater in the S/JR strain than in the R/JR strain, regardless of the treatment. The density of muscarinic cholinergic and calcium channel receptors in the ventricle was not affected by the treatment. The results of this study suggest that the long-term antihypertensive effects of verapamil in the S/JR rat do not involve an alteration in the binding characteristics of adrenergic, cholinergic, or calcium channel receptor sites in ventricular and renal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Dihydropyridine Calcium Antagonists and Agonists in the Isolated Perfused Dahl Rat Kidney

Isolated perfused kidneys from prehypertensive Dahl salt-sensitive (DS) rats demonstrated marginally increased glomerular responsiveness when nitrendipine or verapamil was superimposed upon norepinephrine vasoconstriction. This was manifested by a greater increase in the glomerular filtration rate of DS rat kidneys, as compared to kidneys from Dahl salt-resistant (DR) rats. This glomerular response to nitrendipine by isolated kidneys was not affected by the development of salt-induced hypertension in DS rats, but was eliminated by antecedent salt loading in DR rats. In further experiments designed to assess more directly the reactivity of renal vascular calcium channels in DS and DR rats, the calcium channel agonist BAY-K-8644 and its pure agonist isomer elicited greater increases in renal vascular resistance in kidneys from prehypertensive DS rats than in kidneys from similarly prepared DR rats. Renal vascular reactivity to both BAY-K-8644 and its agonist isomer were greatly magnified following salt-induced DS rat hypertension. These results suggest that a genetically conferred abnormality of calcium channel function may contribute to the renal functional characteristics of the DS rat kidney.

Effect of exercise on the development of salt-induced hypertension in Dahl-S rats.

Male Dahl-S rats were randomly assigned to either normal chow (NC) or high-salt (HS) diets to induce hypertension. Animals were further subdivided into trained (NCT, HST) and untrained (NCN, HSN) groups. Trained groups were exercised on a rodent treadmill 5 days per week for 12 weeks at a constant workload of 26.4 m/min, 5% grade, while duration progressed from 7.5 to 115 min/day. Arterial blood pressure was measured under anaesthesia by direct catheterization of femoral arteries after 4 and 8 weeks, and terminally via the carotid artery. Training resulted in significantly lower systolic and diastolic blood pressure in trained groups compared with untrained. The trained animals also had significantly lower body weights. Analysis of regressed organ weights adjusted for differences in final body weight revealed that the NCT animals had heavier hearts and kidneys than the NCN animals. The HST animals had heavier hearts and lighter kidneys than the HSN animals.