Dietary L-Arginine Attenuates Blood Pressure in Mineralocorticoid-Salt Hypertensive Rats

The present study was designed to investigate the influence of dietary L-arginine supplementation on blood pressure and on ex vivo vascular reactivity in mineralocorticoid-salt (DOCA-salt) hypertensive rats. Systolic blood pressure and heart rate were determined throughout the experimental period in unanaesthetized rats. Plasma and urine electrolyte levels were measured. Vasoconstrictor response to noradrenaline and vasodilator responses to acetylcholine and sodium nitroprusside were evaluated in the isolated perfused mesenteric vascular bed. DOCA-salt hypertensive rats were divided into 2 groups: a control group and a treated group receiving 0.8% L-arginine supplementation in drinking water. Dietary L-arginine supplementation attenuated systolic blood pressure in conscious DOCA-salt hypertensive rats, but did not modify heart rate. Plasma calcium and sodium concentrations and urinary magnesium excretion were decreased by L-arginine supplementation. Noradrenaline-induced vasoconstriction decreased and acetylcholine-induced vasodilatation increased, whereas sodium nitroprusside-induced vasodilatation was not modified, in the L-arginine-supplemented rats. It is concluded that dietary L-arginine supplementation in the diet lowers systolic blood pressure in DOCA-salt hypertensive rats, probably through vascular action.     

高钾饮食对两肾—夹型高血压大鼠血压、肾小球和肾、脾小动脉的影响

用两肾一夹型高血压Wistar大鼠模型观察了高钾饮食对血压、肾小球、肾小管和肾、脾细动脉及小动脉的影响。与普通饮食喂养的高血压大鼠相比,高钾饮食组大鼠血压升高的幅度明显降低(P<0.01),肾小球纤维化和蛋白管型显著减少(P<0.05),高钾组动脉血压的变化与肾细动脉相对内径呈中度负相关(r=-0.575)。提示高钾饮食能抑制两肾一夹型高血压大鼠的血压升高,对肾小球及小脉动有一定的保护作用。     

High calcium diet augments vascular potassium relaxation in hypertensive rats.

The effects of increased dietary calcium on the development of hypertension and vascular smooth muscle responses were studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Both hypertensive and normotensive animals were divided into two groups; the calcium content of the normal diet was 1.1% and that of the high calcium diet 3.1%. During the 12-week study, calcium supplementation significantly attenuated the increase in systolic blood pressure in the hypertensive rats but did not affect blood pressure in the normotensive rats. The contractile responses of endothelium-denuded mesenteric arterial rings to potassium chloride were similar in all study groups. The contractions to norepinephrine were not altered by the high calcium diet either, but smooth muscle sensitivity to this agonist was lower in the normotensive than in the hypertensive rats. Potassium relaxation was used to evaluate the activity of vascular smooth muscle Na+,K(+)-ATPase. The maximal rate of potassium relaxation was fastest in the normotensive groups but was also clearly faster in calcium-treated hypertensive rats when compared with hypertensive rats on a normal diet. Platelets were used as a cell model for the analysis of intracellular free calcium concentration, which was measured by the fluorescent indicator quin-2. Intracellular free calcium was significantly reduced in the hypertensive rats by calcium supplementation and was not affected in the normotensive rats. In conclusion, a reduction of intracellular free calcium concentration indicating improved calcium regulation and a concomitant alteration in vascular relaxation probably reflecting increased activity of smooth muscle Na+,K(+)-ATPase may contribute to the blood pressure-lowering effect of a high calcium diet.     

Relation of plasma renin to end organ damage and to protection of K+ feeding in stroke-prone hypertensive rats

We studied the effects of regular diet (0.35% NaCl/1.1% potassium), high sodium diet (4% NaCl/0.75% potassium), or high sodium and high potassium diet (4% NaCl/2.11% potassium) on blood pressure, plasma renin activity, renal and cerebrovascular lesions, and incidence of stroke and mortality in male stroke-prone spontaneously hypertensive rats (SHRSP). In the first 4 weeks, the rise in blood pressure was higher in high NaCl than in high NaCl/high potassium or regular diet groups. However, by 8 and 12 weeks, the blood pressure in all three groups was similar. After 4 weeks of diet, plasma renin activity was similar in the three groups (3.4 +/- 0.8, 4.1 +/- 0.9, and 5.2 +/- 1.6 ng/ml/hr, in high NaCl, high NaCl/high potassium, and regular diet groups, respectively) and were not related to sodium excretion. After 8 weeks, plasma renin activity was significantly increased only in the high NaCl group (13.7 +/- 3.7 ng/ml/hr), and by 12 weeks plasma renin activity was significantly higher in the high NaCl group (25.3 +/- 3.6 ng/ml/hr) than in the high NaCl/high potassium (11.1 +/- 2.9 ng/ml/hr) or in the regular diet (7.8 +/- 4.6 ng/ml/hr) groups. Moderate to severe renal vascular lesions were first detected in the high NaCl group by 8 weeks of diet. At 12 weeks, renal vascular damage index (RVDI), estimated histologically, was significantly higher in the high NaCl group (RVDI = 79 +/- 14) than in the high NaCl/high potassium (RVDI = 40 +/- 11) and regular diet (RVDI = 7.8 +/- 4.6) groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glomerular and Vascular Lesions in Doca-Salt Hypertension: The Role of Anticoagulation

The aim of the present experiments was to determine if anticoagulant and antithrombotic drugs, which protect against hypertension and vascular damage in some models of hypertension, have a similar effect in DOCA-salt hypertension.

Unilaterally nephrectomized rats received injections of deoxycorticosterone acetate (DOCA) and 1% saline to drink and were treated with either heparin, defibrotide, low molecular weight (LMW) heparin or vehicle (control) for five and a half weeks. At sacrifice heparin treated rats had decreased hematocrit (p<0.001) and prolonged APTT (p<0.001). LMW heparin and defibrotide groups did not differ from control animals in either hematocrit or APTT. The systolic blood pressure (SBP) of heparin treated rats at sacrifice was lower than control (p<0.05) but, there were no other differences in SBP throughout the course of the experiment. Renal morphology revealed a lower number of glomerular epithelial cell droplets in the heparin group (p<0.01) only. Vascular damage did not differ significantly between groups.     

High magnesium diets increase blood pressure and enhance stroke mortality in hypertensive SHRsp rats

The effect of varying amounts of dietary magnesium in conjunction with potassium (K) on hypertension and stroke mortality in hypertensive stroke prone (SHRsp) rats was studied. These results show that high K (2.1%) diets strongly protect against stroke mortality and rises of blood pressure, while high magnesium (Mg) (0.26%) diets appeared to increase stroke mortality and accelerate the rise of blood pressure in SHRsp rats. Similarly, medium-high (1.3%) levels of K in the diet significantly reduced blood pressure and stroke mortality but not nearly as much as the 2.1% K in the high K diet.     

High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats

The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m/day. Calcium supplementation was instituted by increasing the calcium content of the chow from 1.1% to 2.5%. During the 23-week study, calcium supplementation attenuated the rise in blood pressure in both trained and nontrained hypertensive animals, whereas exerise training had no significant effect on blood pressure. The high calcium diet alone was associated with reduced plasma and ventricular tissue contents of atrial natriuretic peptide, both of which were increased by exercise. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Neither increased dietary calcium nor endurance training affected the contractile sensitivity of endothelium-intact preparations to potassium chloride or norepinephrine. However, a high calcium diet enhanced the arterial relaxation induced by the return of potassium to the organ bath upon precontraction with potassium-free solution, and also moderately augmented relaxations to acetylcholine, sodium nitrite, and isoproterenol. Exercise training did not affect the potassium relaxation rate, but enhanced responses to acetylcholine isoproterenol, and sodium nitrite. In conclusion, enhanced arterial potassium relaxation, a response reflecting the function of the vascular sodium pump, paralleled well the long-term blood pressure lowering action of increased dietary calcium intake in exercised and nonexercised hypertensive rats. However, augmented arterial relaxation to agonists could also be observed in the absence of reduced blood pressure following regular physical exercise.     

INCREASED ARGINASE ACTIVITY IN AORTA OF MINERALOCORTICOID-SALT HYPERTENSIVE RATS

The present study was designed, first to investigate aortic arginase activity during the development and the establishment of mineralocorticoid-salt (DOCA-salt) hypertension, and second, to determine the relationship between arginase activity and blood pressure by giving a protein-supplemented diet (50% casein) known to increase hepatic arginase activity. Our results showed that aortic arginase activity in established hypertension of DOCA-salt rats was higher than in normotensive rats. The protein-supplemented diet (50% casein) accelerated the development of DOCA-salt hypertension. There was a positive correlation between arginase activity and the level of blood pressure in these DOCA-salt hypertensive rats fed 50% casein but not in DOCA-salt hypertensive rats on a normal (20% casein) diet. In normotensive rats, the protein-supplemented diet decreased aortic arginase activity and produced no change in systolic blood pressure. Our data suggest that aortic arginase activity is modified in established DOCA-salt hypertension and could participate in the physiopathology of arterial hypertension.     

Effect of Dietary Calcium on In Vitro Aortic Tissue Responsiveness to a Hypertensive Factor

It has been proposed that calcium supplementation in the diet is associated with a reduction in blood pressure. In the present study, we investigated vascular tissue sensitivity to a hypertensive factor (HF) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high calcium diet, a low calcium diet and a food restricted diet. HF, which has been isolated from erythrocytes, increases blood pressure when injected into normotensive rats and stimulates calcium uptake by aortic rings in vitro. Five-week-old rats were divided into the following groups: SHR and WKY fed a regular diet (1% calcium), SHR and WKY fed a high calcium diet (4% calcium), SHR and WKY fed a low calcium diet (0.02% calcium) and SHR and WKY fed a regular diet (1% calcium) in which food intake was restricted to 65% of ad libitum intake. Food intake, body weight, urine phosphate excretion and blood pressure development were followed for 8 weeks. At sacrifice, plasma levels of calcium and phosphate were determined. Tissue responsiveness to HF was calculated by incubating aortic rings from the rats in the different groups with HF and measuring lanthanum-resistant calcium uptake. A 4-fold increase in dietary     

Increased arginase activity in aorta of mineralocorticoid-salt hypertensive rats

The present study was designed, first to investigate aortic arginase activity during the development and the establishment of mineralocorticoid-salt (DOCA-salt) hypertension, and second, to determine the relationship between arginase activity and blood pressure by giving a protein-supplemented diet (50% casein) known to increase hepatic arginase activity. Our results showed that aortic arginase activity in established hypertension of DOCA-salt rats was higher than in normotensive rats. The protein-supplemented diet (50% casein) accelerated the development of DOCA-salt hypertension. There was a positive correlation between arginase activity and the level of blood pressure in these DOCA-salt hypertensive rats fed 50% casein but not in DOCA-salt hypertensive rats on a normal (20% casein) diet. In normotensive rats, the protein-supplemented diet decreased aortic arginase activity and produced no change in systolic blood pressure. Our data suggest that aortic arginase activity is modified in established DOCA-salt hypertension and could participate in the physiopathology of arterial hypertension.     

Role of sympathetic nerve activity and natriuresis in the antihypertensive actions of potassium in NaCl hypertension

Although the precise mechanism of the antihypertensive action of potassium remains controversial, the natriuretic property of potassium is thought to play an important role. Since the renal nerves have been shown to control urinary sodium excretion, the present study was performed to clarify the role of the sympathetic nervous system in the antihypertensive effect of potassium supplements in DOCA-salt hypertensive rats and in salt-sensitive hypertensive patients. Supplements of a 0.2% or a 1% KCl were able to moderate the development of the DOCA-salt hypertension dose-dependently, in combination with natriuresis. Renal norepinephrine turnover was markedly accelerated in the DOCA-salt rats as compared with the control rats, but the potassium supplements normalized it. Eleven patients, who had taken the potassium supplement (96 mEq/day) on a high-sodium diet, showed a lesser increase in mean blood pressure with sodium loading than 12 patients who did not take the potassium supplement. With a high-sodium diet, the potassium-supplemented patients retained less sodium and showed a lesser increase of plasma volume and cardiac output, and their adrenergic nervous activity was relatively lower during the early period of salt loading. Moreover, in salt-sensitive patients the potassium supplement was more effective for preventing a rise in blood pressure with sodium loading than in non-salt-sensitive ones. These results suggest that potassium may attenuate the rise in blood pressure during the DOCA-salt treatment in the rat and during sodium loading in salt-sensitive patients, mainly as a result of inhibiting sodium retention due to increased renal sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats

The effect of the combined ET_A/ET_B endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 ± 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 ± 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambigously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension.     

Function of the isolated perfused kidneys from young or adult rats with post-DOCA-salt hypertension.

The function of isolated perfused kidneys in post-DOCA phase of DOCA-salt hypertension was evaluated in rats subjected to DOCA-salt treatment either from youth or only in adulthood. Post-DOCA-salt hypertension was more severe in young than in adult animals. Kidneys isolated from young post-DOCA-salt hypertensive rats had higher renal vascular resistance when compared to adult ones. Perfusion of isolated kidneys over a wide range of perfusion pressure (110-170 mm Hg) has shown similar decrease of glomerular filtration, filtration fraction, diuresis and natriuresis in both age groups of DOCA-salt treated groups. Perfusion pressure-sodium excretion curves had reduced slope and were shifted to the right in both hypertensive groups, indicating huge glomerular damage. Nevertheless, the relative difference in glomerular filtration and sodium excretion between hypertensive rats and age-matched normotensive controls was always greater in younger animals. These results suggest that the more pronounced changes in glomerular hemodynamics and filtration could be involved in higher blood pressure-response of young animals to DOCA-salt treatment.     

Sugar-induced hypertension in Fischer 344 and F1-hybrid rats (F344/BN) at different ages

Epidemiological evidence suggests that some nutrients, like sodium and potassium, participate in age-related hypertension. A role for refined carbohydrates (CHO), principally sugar, in blood pressure regulation is not generally recognized. This may be unfortunate, since modern lifestyle is associated with large amounts of dietary refined CHO. We examined the effect of a high sugar diet on systolic blood pressure (SBP) in Fischer 344 rats (F344) and the F1-hybrid of this strain (F344/BN). These genotypes have been used to develop experimental models for studies on different aspects of aging. Age-dependent hypertension has not been reported in either strain. In fact, insensitivity to salt-induced hypertension has been found in F344 rats. Upon arrival at our laboratory, the mean difference in SBP between the youngest (4 months) and oldest (18 months) F344 and F1-hybrid rats was 10 mm Hg, the highest mean SBP was 123 mm Hg. These values remained relatively constant over the next month when both strains consumed a low sugar diet. Differently, a steady increase in SBP occurred in both strains when rats of all ages were fed a diet high in sucrose content, mean SBP increasing to over 170 mm Hg at termination of study. Older rats proved more sensitive initially to sugar-induced SBP elevations. Associated with rising SBP was evidence of Na retention. We conclude that a diet containing excess sugar can create a gradual elevation of SBP into a hypertensive range with aging of F344 and F1-hybrid rats. This contrasts with previous findings.     

Lowering of blood pressure improves endothelial dysfunction by increase of nitric oxide production in hypertensive rats.

To investigate the effects of angiotensin converting enzyme inhibitor (ACE-I) and other antihypertensive agents on the nitric oxide (NO) release during hypertension, seven- and fourteen-week-old SHR and deoxycorticosterone acetate (DOCA)-salt rats were treated with hydralazine, manidipine (Ca antagonist) or quinapril (ACE-I) for 3 weeks to lower blood pressure. Systolic blood pressure (SBP) was measured by the tail cuff method once each week. Endothelial cells (ECs) derived from the descending aorta of the treated rats were cultured and NOx levels in culture media were measured with an NO analyzer based on the Griess reaction. In both SHR and DOCA-salt rats, antihypertensive therapy lowered SBP to levels similar to those of control rats. The only exception was quinapril treatment of DOCA-salt rats. Although NOx release by ECs derived from hypertensive rats was improved by antihypertensive therapy, the effect was most pronounced in SHR treated with quinapril. In addition, restoration of NOx release was much more remarkable in younger SHR. NOx release was significantly higher in DOCA-salt rats treated with quinapril than in control rats without reduction of SBP. These results suggest that lowering blood pressure improves release of NO by ECs during hypertension and that the time at which antihypertensive therapy is started is also important to preserve endothelial function. Furthermore, ACE-I is suggested to protect endothelial function by increasing NO production in addition to lowering blood pressure.     

Vasoactive effects of potassium in kidneys of hypertensive rats fed a high-potassium diet.

DESIGN AND METHODS: Levels of dietary and serum potassium are thought to correlate inversely with vascular resistance and blood pressure. This study examined renal vascular resistance in perfused rat kidneys partially preconstricted with 10 micromol/ phenylephrine, quantifying changes in the resistance when levels of potassium in the perfusate ([K+]o) were varied between 2 and 80 mmol/l. RESULTS: In kidneys from 17-week-old Wistar-Kyoto rats (WKY strain) fed a normal diet (American Institute of Nutrition AIN-76 diet), the resistance decreased when [K+]o was raised from 4 to 6-20 mmol/l, whereas resistance increased when [K+]o was either lowered to 2 mmol/l or raised above 25 mmol/l. The vasodilation that occurred at 13 mmol/l [K+]o was blocked by 100 micromol/l BaCl2 and 10 micromol/l ouabain in an additive manner, suggesting that both the inward rectifier K+ channel and the Na-K-ATPase underlie the dilation. Kidneys from spontaneously hypertensive rats (SHR strain) fed the AIN-76 diet displayed modestly enhanced vasodilations and vasoconstrictions as compared to WKY. A high-potassium diet (AIN-76 supplemented with 3.5% potassium citrate, provided for 8 weeks) led to exaggerated vasoconstrictive effects of [K+]o, and modestly enhanced vasodilations, in WKY rats. In contrast, the diet led to attenuated vasoconstrictions, and dramatically enhanced vasodilations, in the SHR strain. The diet did not affect the blood pressure increase or weight gain of either strain. CONCLUSIONS: Changes in the responsiveness of blood vessels to extracellular potassium might underlie some beneficial effects of high-potassium diets in hypertensive individuals.     

High potassium diet augments endothelium-dependent relaxations in the Dahl rat

Endothelium-dependent relaxations are reduced in hypertensive rats. High dietary potassium supplementation reduces the incidence of strokes in Dahl rats independently of blood pressure, thereby suggesting a direct protective effect of the diet. Endothelium-dependent relaxations and aortic vascular architecture were studied in Dahl salt-sensitive rats fed 8% NaCl, 0.1% NaCl, or 8% NaCl plus 3.6% potassium citrate for 8 weeks. Rats fed 8% NaCl or 8% NaCl plus 3.6% potassium citrate became hypertensive, while those fed 0.1% NaCl did not. Aortic rings with and without endothelium were suspended in organ chambers filled with physiological salt solution (37 degrees C) and aerated with 95% O2, 5% CO2. In rings contracted with norepinephrine, acetylcholine and adenosine 5'-diphosphate caused endothelium-dependent relaxations that were significantly reduced in rats fed 8% NaCl as compared with those fed 0.1% NaCl. Potassium supplementation (8% NaCl/3.6% potassium citrate) significantly enhanced relaxations to acetylcholine in salt-sensitive rats, while those to adenosine 5'-diphosphate and thrombin were either minimally affected or unchanged. Relaxations to sodium nitroprusside were similar in rats with or without potassium supplementation. Hypertension significantly increased aortic medial and intimal thickness. Dietary potassium had no significant effect on the vascular architecture. These results suggest that high potassium diet enhances endothelium-dependent relaxations in Dahl rats at least in part independently of changes in blood pressure. Thus, potassium may be important for its protective effect against stroke and renal damage in this animal model of hypertension.     

Dietary Sodium Intake and Urinary Dopamine and Sodium Excretion During the Course of Blood Pressure Development in Dahl Salt-Sensitive and Salt-Resistant Rats

ABSTRACT

Recent studies have suggested that dopamine (DA) formed within the kidney may play an important role in promoting sodium excretion, and that renal production and excretion of DA is determined by dietary sodium intake. Inasmuch as increased sodium consumption produces hypertension in Dahl salt-sensitive (DS) rats but not in Dahl salt-resistant (DR) rats, the present study was designed to examine the relationship between sodium consumption and urinary excretion of DA in these rats. DS and DR rats were placed on either high sodium chloride (8%) or low sodium chloride (0. 4%) diets at 4 weeks of age and their systolic blood pressure (SBP), urine volume, urinary sodium and catecholamine excretion were measured once every week for the next 4 weeks. High sodium chloride diet increased SBP in DS rats at 6 weeks of age and SBP continued to rise until they were 8 weeks old. The SBP of DR rats did not reach hypertensive levels when they were given high sodium chloride diet. The SBP of DS rats on low sodium chloride diet was significantly higher than DR rats on the same diet. The urinary DA excretion increased with age in all four groups of rats and was similar when they were 8 weeks old. However, both DS and DR rats on high sodium chloride diet excreted greater amounts of sodium and had increased urine volume compared to the DS and DR rats on low sodium chloride diet. There were no significant differences in urinary NE or E excretion in these four groups of rats. Kidney levels of DA and NE were significantly lower in DS compared to DR rats on high sodium chloride diet. These results show that although there are no differences in urinary DA excretion between rats on low and high sodium intake, both DS and DR rats on high sodium chloride diet are able to exhibit a natriuretic response. The DS rats eliminate sodium at the expense of an elevated SBP whereas DR rats stay normotensive. Therefore, it appears that alterations in mechanisms controlling renal vascular resistance rather than sodium excretion are responsible for the development of hypertension in DS rats.     

Decreased density of vascular receptors for atrial natriuretic peptide in DOCA-salt hypertensive rats

We have previously found that vascular receptors for atrial natriuretic peptide (ANP) in the rat are down-regulated by volume expansion. For this reason vascular ANP receptor density and affinity were examined in a model of volume-expanded hypertension, the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The density of mesenteric vascular ANP binding sites was decreased in DOCA-salt hypertensive rats from a control value in uninephrectomized rats of 203 +/- 25 fmol/mg protein to 60 +/- 13 fmol/mg protein (p less than 0.01). The sensitivity of norepinephrine-precontracted aorta to ANP was significantly reduced in DOCA-salt hypertensive rats (p less than 0.001). DOCA-salt hypertensive rats infused intravenously for 4 days with ANP, 100 to 300 ng/hr, did not experience a lowering of blood pressure, in contrast to the significant reduction in blood pressure seen in two-kidney, one clip Goldblatt hypertensive rats similarly infused. In the latter there was no natriuretic response to ANP, while in the DOCA-salt hypertensive rats natriuresis occurred without lowering of blood pressure. In the DOCA-salt hypertensive rats plasma ANP concentration was increased to 68 +/- 8 fmol/ml from 10 +/- 1 fmol/ml in uninephrectomized rats. In conclusion, raised ANP concentration in plasma of volume-expanded hypertensive rats (DOCA-salt hypertension) may result in decreased density of ANP vascular receptors. These results suggest that a decrement in the number of ANP receptors may be a cause of decreased sensitivity of vascular responses to ANP in vitro and resistance to the blood pressure-lowering action of ANP in vivo.     

In SHR Rats,Dietary Potassium Determines NaCl Sensitivity in NaCl-Induced Rises of Blood Pressure

The current study tested whether the spontaneously hypertensive rats (SHR) from Charles River Laboratories are resistant or not to NaCl-induced rises of blood pressure and deaths. These rats are fairly NaCl-resistant on a 2.1% high K diet, whereas they are quite susceptible to NaCl-induced hypertension and deaths on a 0.5% normal K diet. Thus, a high K diet strongly protects against a NaCl-induced rise of blood pressure as well as deaths in these SHR rats. Hence the level of dietary K determines the degree of NaCl sensitivity in these SHR rats.