Dietary Salt Loading Research Articles

Altered responses of aortic smooth muscle from Sprague-Dawley rats with salt-induced hypertension.

1. The contractile responses of aortic ring preparations from Sprague-Dawley rats made hypertensive by 6-week dietary salt loading were studied. The test and control diet contained 8.0 and 0.3% NaCl, respectively. Aortic rings from salt-loaded rats showed enhanced sensitivity to noradrenaline (NA) but not to serotonin. Contractile responses to CaCl2 in Ca-free NA-containing medium was significantly enhanced in salt-loaded rats, but was unchanged in K(+)-depolarised medium. K(+)-induced relaxation (a functional indicator of Na-K adenosine triphosphatase activity) was sensitive to 10 mumol/L ouabain and was significantly attenuated in aortic rings from salt-loaded rats. The results suggest that hypertension induced by salt-loading is associated with enhanced sensitivity to NA, increased Ca2+ entry through receptor-operated channels, and impairment of Na-K ATPase enzyme activity.

High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension.

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of tubuloglomerular feedback by the D1 agonist fenoldopam in chronically salt‐loaded rats.

1. Chronic dietary NaCl loading in rats is paralleled by an increase of the dopamine concentration in the tubular fluid and humorally mediated inhibition of the tubuloglomerular feedback mechanism at the macula densa. Since these two phenomena are causally linked, the alterations in the tubuloglomerular feedback response by the luminal application of dopamine, the D1 agonist fenoldopam, the D2 agonist bromocriptine and the D1 and D2 antagonists SCH 23390 and metoclopramide were further investigated using the micropuncture technique. 2. Very similar, concentration-dependent inhibition of the tubuloglomerular feedback response was observed for dopamine and fenoldopam. Half-maximal inhibition was achieved at 10(-11) M and the slope factors of the sigmoid concentration-response curves were comparable. Bromocriptine was ineffective. 3. The inhibition of TGF by both agonists could be antagonized very similarly and concentration dependently by the D1 antagonist SCH 23390. At equimolar concentrations of 10(-9) M the inhibition was reduced by approximately 50%. Raising the SCH 23390 concentration to 10(-6) M completely abolished the TGF inhibition. In contrast, TGF inhibition by 10(-9) M-fenoldopam or dopamine was not significantly affected by an equimolar concentration of the D2 antagonist metoclopramide. Increasing metoclopramide concentration to 10(-6) M attenuated tubuloglomerular feedback inhibition by approximately 55%. 4. It is concluded that the inhibition of tubuloglomerular feedback seen during chronic dietary salt loading can be ascribed to the binding of endogenous dopamine to luminal D1 receptors on the macula densa cells.

Endogenous dopa and dopamine responses to dietary salt loading in salt-sensitive rats

We measured daily urinary excretion rates of dopamine and dopa during dietary salt loading and natriuretic responses to exogenous dopamine in Dahl salt-sensitive (DS), Dahl salt-resistant (DR) and Sprague-Dawley rats. Excretion rates of dopa increased approximately sixfold during salt loading in all rat strains. Maximal urinary dopa responses were attained within 1 day of salt loading. Daily excretion rates of dopamine also increased about five- to sixfold in DS and DR rats and about twofold in Sprague-Dawley rats, with maximal dopamine responses attained by day 5. Dopamine infusion (3 micrograms/kg per min) increased urinary sodium excretion by 406 +/- 132 % (mean +/- s.e.m.) in Sprague-Dawley rats but only 267 +/- 131% and 147 +/- 80% in DS and DR rats (P less than 0.05 for Sprague-Dawley versus Dahl rats). The results demonstrate that salt loading markedly and rapidly increases dopa excretion in rats. Considering values for dopamine excretion in other rat strains, the results suggest that Dahl rats have increased formation of dopamine for a given amount of dopa delivery to the kidney and that this abnormality is unrelated to salt-sensitive hypertension in DS rats. The results also provide in vivo support for the view that the responsiveness of renal dopamine receptors mediating natriuresis is related to production of endogenous dopamine in the kidney.

Hemodynamic response to dietary sodium loading in essential hypertension studied with Doppler echocardiography.

The cardiac response to dietary salt loading was assessed by Doppler echocardiography during various sodium intakes (52-345 mEg per day) in 30 patients with essential hypertension. The Mitral flow velocity integral in the rapid filling phase (IntR) and the atrial contraction phase (IntA) was measured from the transmitral flow pattern, and the sum of IntR and IntA (IntR + IntA), the ratio of IntA to IntR (IntA/IntR), cardiac output (CO) and total peripheral resistance (TPR) were calculated. With salt loading, the mitral flow pattern remained almost unchanged in the nonsalt-sensitive (NSS) patients. Fourteen of the 19 salt-sensitive (SS) patients showed significant increases in IntR + IntA and CO with salt loading (IntR + IntA, from 13.9 +/- 2.8 to 17.9 +/- 3.6 cm, p less than 0.01; CO, from 6021 +/- 2130 to 8305 +/- 1699 ml/min, p less than 0.01), and were termed "salt-sensitive CO-dependent" (SS [COdep]), suggesting that the apparent pressor response to sodium loading was mediated by an increased CO. In the remaining five SS patients termed "salt-sensitive CO-independent" (SS [COindep]), IntA/IntR increased significantly with sodium repletion (from 0.66 +/- 0.23 to 0.90 +/- 0.31, p less than 0.01), without a significant change in IntR + IntA. Increments in IntA/IntR observed in the SS [COindep] patients were considered to be due to an elevation of total peripheral resistance (TPR), since changes in IntA/IntR were significantly correlated with those in TPR in all subjects (r = 0.617, p less than 0.01).

Increased spillover of dopa into arterial blood during dietary salt loading

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused L-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.

Salt-sensitive blood pressure and exaggerated vascular reactivity in the hypertension of diabetes mellitus

purpose: This study evaluates the effects of dietary salt restriction and loading on blood pressure in normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM). Salt sensitivity of blood pressure responses is compared to vascular reactivity to infused angiotensin II on the two sodium diets. patients and methods: We studied 19 patients with NIDDM (seven normotensive, 12 hypertensive) and seven nondiabetic control subjects under metabolic balance after 6 days on a constant low-(20 mEq) sodium diet and again after 6 days on a high- (250 mEq) sodium diet. Salt sensitivity of blood pressure was determined by the increment in integrated 24-hour blood pressure values on changing from the low- to the high-sodium diet. Blood pressure and plasma aldosterone responses to a graded-dose infusion of angiotensin II were also examined on both sodium diets. results: Eight of 12 hypertensive patients with NIDDM displayed salt-sensitive blood pressure responses, whereas none of the normotensive patients with NIDDM or control subjects were salt-sensitive. Patients with NIDDM also had augmented blood pressure responses to infused angiotensin II on both sodium diets when compared to control subjects. Whereas controls had reduced vascular responses to angiotensin II on the low-sodium diet, these responses were not decreased in patients with NIDDM. Patients with NIDDM also retained more sodium on the high-sodium diet than did the control subjects. conclusion: Hypertension in patients with NIDDM is frequently salt-sensitive, which may be due to sodium retention and enhanced vascular reactivity to angiotensin II. Since sodium restriction does not normally reduce vascular reactivity to angiotensin II in NIDDM, salt-restricted diets may be less effective in blood pressure control in hypertensive NIDDM.

老年者本態性高血圧症における食塩負荷時の心拍出量及び末梢局所血流分布の解析

Hemodynamic changes with dietary salt loading were assessed by Doppler echocardiography during different sodium intake (7 g/day for 8 weeks, 20 g/day for 1 week) in 29 elderly patients with essential hypertension (81.6 +/- 6.7 years, 4 men, 25 women). With salt loading, 24 patients whose mean blood pressure (MBP) increased by 10% or more were defined as salt sensitive (SS) group, and 5 patients whose MBP did not change, or increased by less than 10% were defined as non-salt sensitive (NSS) group. Based on the mitral flow velocity integral, cardiac output (CO) was calculated, and total peripheral resistance (TPR) was calculated as MBP divided by CO. Nine of the 24 SS patients were termed "SS (COdep)" whose CO increased significantly with salt loading. In the remaining 15 SS patients termed "SS (TPRdep)", TPR increased significantly with sodium repletion. Blood flow in the common carotid, superior mesenteric, or terminal aorta was calculated from each flow velocity integral. The percent change in peripheral resistance calculated by dividing MBP by each blood flow was obtained. There were no significant percent changes in the common carotid resistance in SS (COdep), SS (TPRdep) or NSS groups. The superior mesenteric resistance increased significantly in all three groups. The terminal aortic resistance increased in the SS (TPRdep) group, but decreased in the SS (COdep) or NSS group. These results indicate that salt sensitivity is ascribable to changes in regional vascular resistances.

Das atriale natriuretische Peptid und seine Bedeutung für die arterielle Hypertonie

Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.

Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans

1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.

Salt Increases Blood Pressure with Biphasic Changes in Hypothalamic Responsiveness in Rats

Tail-cuff systolic pressures became elevated in male Wistar rats fed chow containing 8% NaCl for 4 weeks. After 4 weeks of salt loading, pressor and sympathetic responses to ventromedial hypothalamic stimulation were larger in salt-loaded rats. When similar experiments were done following sinoaortic denervation, all of the effects previously induced by dietary salt loading persisted. By contrast, after only 1 week of salt loading, pressor and sympathetic responses to hypothalamic stimulation were reduced, instead of being increased. Since circulating plasma volume was increased in week 1, it was considered possible that reduced hypothalamic responsiveness was due to enhanced cardiopulmonary baroreflexes. Supporting this interpretation, bilateral vagotomy reversed the hypothalamic inhibition occurring in week 1. Although neither the site nor mechanism causing sympathetic hyperactivity has been determined, our results indicate that chronic dietary salt loading has biphasic effects on the ventromedial hypothalamus: an initial inhibition in the first week followed by stimulation thereafter. These results could mean that dietary salt loading eventually increases sympathetic activity and thereby induces hypertension by stimulating the ventromedial hypothalamus.

The control of glomerular filtration rate and renal blood flow in chronically volume-expanded rats.

1. Chronic volume expansion by dietary salt loading practically abolishes tubuloglomerular feed-back (TGF) by means of a humoral inhibitor in tubular fluid. Elimination of the vasoconstrictor influence of feed-back does not, however, increase glomerular filtration rate (GFR) and renal blood flow (RBF), implying that chronic salt loading induces additional preglomerular vasoconstriction. This being so, the feed-back response which, although absent in free-flowing nephrons, can still be elicited by loop of Henle perfusion with Ringer solution, should be essentially normal, except that nephron GFR at any loop perfusion rate should be lower than in controls. Persistence of RBF, GFR and nephron GFR autoregulation would imply that autoregulation is achieved by a preglomerular resistance control system independent of feed-back. 2. These hypotheses were tested by clearance and micropuncture experiments in rats chronically fed a diet containing 40 g NaCl (kg food)-1. 3. RBF and GFR autoregulation indeed persisted, the former down to 90 mmHg compared with 105 mmHg in controls. In controls, nephron GFR measured distally was autoregulated down to 90 mmHg whereas that measured proximally was autoregulated only above 105 mmHg. In high-salt rats nephron GFR from both sites was autoregulated to 90 mmHg. 4. Loop of Henle perfusion with homologous tubular fluid in high-salt rats confirmed attenuation of feed-back. Loop perfusion with Ringer solution yielded a response comparable to that in controls (maximal reduction of nephron GFR to 57%, compared with 56% in controls). Absolute nephron GFR at any loop perfusion rate was lower in high-salt rats than in controls. 5. These observations confirm the initial hypotheses. Considering feed-back and autoregulation as independent, preglomerular resistance control mechanisms, together with elementary haemodynamic considerations, allows formulation of a renal haemodynamics model whose quantitative predictions regarding characteristics of RBF, GFR and feed-back control are remarkably consistent with the literature.

Resetting of tubuloglomerular feedback in acute volume expansion in rats.

Loss of sensitivity or "resetting" of tubulo-glomerular feedback has been reported after both acute and chronic volume expansion in rats. In chronic volume expansion due to dietary salt loading, resetting was found to result from the appearance of an inhibitory factor in tubular fluid. The aim of the present study was to test the possibility that resetting after acute isooncotic volume expansion may also be due to such an inhibitor. Rats were acutely volume expanded (4.5% of body weight) by infusion of a solution of fresh plasma and Ringer's solution. Tubuloglomerular feedback activity was assessed in expanded and control animals by measuring early proximal flow (EPF) rate during perfusion of the loop of Henle at varying rates with proximal tubular fluid harvested from the control (control TF) and expanded animals (AVE TF). When loops of Henle in control animals were perfused with control TF at 10, 20 or 40 nl min-1, EPF fell from (mean +/- SD) 29.8 +/- 5.6 at zero loop flow to 27.5 +/- 7.5, 21.1 +/- 4.2 and 15.5 +/- 4.5 nl min-1 gKW-1 respectively. Perfusion at the same rates with control TF in expanded animals reduced EPF from 39.5 +/- 9.6 (at zero loop flow) to 35.9 +/- 11.3, 31.6 +/- 4.3 and 22.9 +/- 6.8 nl min-1 gKW-1 respectively. When loops of Henle in control animals were perfused with AVE TF, EPF fell from 28.6 +/- 9.5 (zero loop flow) to 23.5 +/- 8.6, 19.9 +/- 8.2 and 15.6 +/- 6.5 nl min-1 gKW-1 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary salt and cholesterol loading on vascular adrenergic receptors.

To evaluate the effects of salt and cholesterol intake on vascular responses to catecholamines, alpha 1- and beta-adrenergic receptor densities were determined in control, cholesterol-loaded, salt-loaded with desoxycorticosterone acetate (DOCA) and furosemide-loaded male rabbits, using [3H]-prazosin and (-)-[125I]-cyanopindolol as ligands, respectively. In the aortic membrane, the density of alpha 1-adrenergic receptors (Bmax = 120 +/- 14 fmol/mg protein, Kd = 0.48 +/- 0.05 nM) was higher than that of beta-adrenergic receptors (Bmax = 10.5 +/- 1.7 fmol/mg protein, Kd = 47.1 +/- 8.6 pM). Salt loading and depletion did not alter the density or affinity of either the alpha 1- or beta-adrenergic receptors. By contrast, cholesterol loading significantly decreased alpha 1-adrenergic receptor affinity to a Kd value of 0.81 +/- 0.11 nM from the control level of 0.48 +/- 0.05 and increased the beta-adrenergic receptor density to a Bmax of 18.7 +/- 1.9 fmol/mg protein from the control level of 10.5 +/- 1.7. These results showed that the density of alpha 1-adrenergic receptors was higher than that of beta-adrenergic receptors in the rabbit aortic membrane preparation, and suggested that the sensitivity of aortic membrane to catecholamines was changed by cholesterol loading.

Calcium metabolism, renin activity, and the antihypertensive effects of calcium channel blockade

Although abnormalities of calcium metabolism have been described in various hypertensive states, the specific manner in which these abnormalities contribute to the increased pressure remains unclear. Our own group, in attempting to resolve the seemingly contradictory evidence thus far obtained, has adopted an approach emphasizing the clinical as well as biochemical heterogeneity among hypertensive subjects. We have observed the following: (1) broadbased deviations of calcium ionic and hormonal indices in patients with essential hypertension; (2) these deviations are linked with concurrent deviations in the renin-aldosterone system. Thus, low-renin subjects exhibit a calcium ionic and hormonal profile suggestive of calcium deficiency, whereas high-renin subjects have an opposite metabolic profile suggestive of calcium excess; (3) blood pressure responses to dietary salt loading may also differ among renin subgroups of essential hypertension and may be mediated by salt-induced alterations of calcium metabolism. In the absence of these alterations, dietary salt intake results in little or no change in blood pressure; and (4) calcium as a dietary supplement may itself possess antihypertensive properties in targeted subgroups of essential hypertensive patients, preferentially in low-renin, lower ionized calcium subjects. Interestingly, calcium channel blockade also preferentially lowers pressure in low-renin, lower serum ionized calcium forms of hypertension and may define those subjects whose elevated pressure is most dependent on extracellular calcium. Conversely, renin profiling or serum ionized calcium measurements may be used clinically to help target subjects most likely to benefit from calcium channel antagonists. Lastly, unlike other antihypertensive drug classes, high salt intake does not blunt, and may even enhance, the hypotensive effects of calcium channel blockade, lessening the need for stringent dietary recommendations. Altogether, these heterogeneous alterations of calcium metabolism in essential hypertension suggest that the linkage between the regulation of calcium metabolism, renin system activity, and blood pressure in essential hypertension is of pathophysiologic as well as therapeutic relevance.

Effects of dietary sodium chloride loading on parathyroid function, 1,25-dihydroxyvitamin D, calcium balance, and bone metabolism in female rats during chronic prednisolone administration.

The effects of dietary sodium chloride supplements (8 g/100 g diet) on parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], calcium balance, bone metabolism, and bone composition were studied in rats treated with prednisolone (2 mg/kg w X day) for 12 weeks. Animals on a low calcium diet (0.1% Ca) received the following treatments: group 1, control; group 2, NaCl; group 3, prednisolone; group 4, NaCl plus prednisolone. Parathyroid function was assessed indirectly from urinary cAMP excretion: bone resorption was estimated by studying urinary hydroxyproline excretion and mobilization of 45Ca from bone. Dietary salt loading increased the urinary excretion of calcium, 45Ca, cAMP, and hydroxyproline and raised serum 1,25-(OH)2D and net calcium absorption, but lowered calcium retention, femoral calcium, and total body calcium. Prednisolone slowed body growth and lowered net calcium absorption, calcium retention, femoral calcium, and total body calcium. Urinary calcium excretion was higher in rats receiving salt and prednisolone in combination than in animals taking salt without prednisolone, but other responses to salt and prednisolone were independent. Thus, salt and prednisolone each elicit osteopenia, and salt causes bone loss in rats receiving prednisolone. The osteopenic effect of salt is attributed to primary augmentation of urinary calcium excretion and secondary increases in PTH-medicated bone resorption. Although salt-treated rats have higher blood levels of 1,25-(OH)2D, bone loss occurs because alimentary calcium absorption is not elevated sufficiently to offset urinary calcium losses. Prednisolone lowers bone formation and net calcium absorption without lowering serum 1,25-(OH)2D values. The parathyroid-vitamin D axis remains intact in prednisolone-treated rats, as they show increases in PTH and 1,25-(OH)2D after salt treatment.

Increased voluntary ethanol intake after dietary salt-loading in rats.

The effect of dietary salt-loading on selection for 5% ethanol compared with dilute solutions of citric acid was examined in 9 male rats. Compared with 9 control rats maintained on a normal diet, salt-loaded rats exhibited significant increases in ethanol consumption and ethanol selection. Selection for ethanol remained elevated after resumption of the normal diet.

The syndrome of hypertension and hyperkalaemia with normal GFR. A unique pathophysiological mechanism for hypertension?

Based on 28 reported patients, constant features of the syndrome of hypertension and hyperkalaemia are hyperkalaemia, hyperchloraemia, normal renal glomerular function and, in all adult patients, hypertension. Inconstant features include short stature, intellectual impairment and muscle weakness. Levels of renin and aldosterone are low, but respond to dietary salt restriction and diuretic therapy, both of which reverse the hypertension and hyperkalaemia. The basic abnormality is excessive renal sodium retention, leading to chronic suppression of renin and aldosterone; the latter is then hyporesponsive to the hyperkalaemic stimulus. Dietary salt loading or impaired production of any natriuretic or chloriuretic factor (for example atrial natriuretic peptide or renal natriuretic prostaglandins) would predispose to development of the syndrome. With normal GFR, this appears to be a unique mechanism for hypertension and hyperkalaemia.

Renin, calcium metabolism and the pathophysiologic basis of antihypertensive therapy

The renin-angiotensin-aldosterone system regulates blood pressure and volume homeostasis in addition to sodium and potassium metabolism, and may be linked to divalent cation metabolism as well as hypertensive disease. In essential hypertension, circulating serum magnesium and Ca ++, and the calcium regulating hormones, parathyroid hormone, calcitonin and 1,25 dihydroxyvitamin (1,25D) are different in the various renin subgroups. Elevated blood pressure induced by such maneuvers as dietary salt loading is associated with exacerbations of these calcium metabolic deviations, and appears related to salt-induced changes in serum Ca ++ or 1,25D levels. Short- or longer-term lowering of blood pressure with the calcium-channel blocker, nifedipine, or with calcium or magnesium supplementation is associated with a shift of renin system activity and calcium metabolic indexes back to average normotensive values in those subjects most susceptible to these hypotensive agents. These observations suggest that deviations in calcium metabolism in essential hypertension may be related to the pathophysiology of the hypertensive process. Further, renin system activity and calcium metabolic indexes such as serum Ca ++ levels may help target specific subgroups of hypertensive populations most susceptible to various dietary or drug maneuvers, and thus may provide a basis to better understand and treat clinical hypertension.

Dietary salt loading produces baroreflex impairment and mild hypertension in rats.

Mild hypertension with reduced chronotropic baroreflex sensitivity to phenylephrine occurred in Sprague-Dawley rats fed a high-salt diet for 5 wk. Progressive elevation of systolic and mean pressures, detected initially by indirect tail-cuff measurement, was later verified by direct recording of phasic pressures from indwelling aortic catheters in the same rats. Reflex bradycardia during pressor responses to phenylephrine was consistently less pronounced in salt-loaded than in control rats, whether tested while rats were awake or anesthetized. However, attendant decreases in renal nerve activity were not appreciably altered. Neither central nor carotid baroreceptor mechanisms were considered likely but aortic baroreceptors must have somehow been depressed because increases in afferent aortic nerve activity elicited during intravenous infusion of phenylephrine were invariably smaller in salt-loaded than in control rats. Whatever the underlying mechanisms may be, our results show that when hypertension develops during dietary salt loading, baroreflex chronotropic responses are selectively inhibited while attendant decreases in renal nerve activity are preserved.