Calcium and blood pressure regulation in normal and hypertensive subjects.

Abstract

To elucidate the mechanisms involved in calcium-mediated blood pressure (BP) control, plasma norepinephrine (NE), epinephrine, renin activity, and angiotensin II (AII) levels and the cardiovascular pressor responsiveness to NE and AII were assessed before and during acute mild hypercalcemia or short-term calcium (Ca) inhibition with nifedipine in 20 normal and five borderline hypertensive subjects. In normal subjects, systolic BP and plasma NE and epinephrine concentrations were increased significantly (p less than 0.05) during an acute rise in serum Ca of 3.1 mg/dl (intermediate rate Ca infusion, 0.05 mg/kg/min for 3 hours), but not following an increase of 1 mg/dl (low rate Ca infusion, 0.034 mg/kg/min for 2 hours). In the borderline hypertensive group, low-rate Ca infusion elevating serum Ca by 1 mg/dl was associated with a slight increase in systolic BP (p less than 0.05) and plasma catecholamines. In both groups, the pressor responses to infused NE and AII, and plasma renin and AII levels, were unchanged during mild to moderate hypercalcemia. Nifedipine given for 2 weeks (average dose, 48 mg/d) reduced BP significantly (p less than 0.05) in the borderline hypertensive subjects only and NE pressor responses in both groups (p less than 0.025), but had no significant effect on plasma catecholamines, renin, or AII levels. These findings suggest that the adrenergic BP control mechanism may be more dependent on clinical variations in calcium metabolism than the angiotensin BP regulatory mechanism. Acute hypercalcemia may increase BP at least in part by causing an increase in adrenergic activity without an equivalent decrease in cardiovascular reactivity. Calcium inhibition with nifedipine may modify noradrenergic BP control by lowering the NE pressor reactivity without causing an equivalent increase in adrenergic activity.

Converting‐enzyme inhibition buffers the counter‐regulatory response to acute administration of nicardipine.

“…Three hours after the second dose this inhibition was more marked (-98%) and it was associated with a slight but significant fall in diastolic BP, recorded by an 500 - automatic device, without tachycardia, and a further increase in active and inactive renins. Intravenous nicardipine administration induced a significant fall in BP with and without inhibition of converting-enzyme activity (Figure 2), suggesting that calcium antagonist vasodilation in healthy normotensive men is not influenced by the plasma level of angiotensin II as it has been suggested in normotensive and hypertensive patients during exogenous angiotensin II and noradrenaline infusions (Bianchetti et al, 1983;Simon & Snyder, 1984).…”

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents.

“…10 In addition, the regional circulation in different areas, such as limb 8 and forearm, 9 appears to be more sensitive in hypertensive than in normotensive subjects to the arteriolar dilation induced by verapamil. Since this phenomenon has not been observed with nonspecific vasodilators such as nitroprusside, 9 it has been speculated that calcium entry blockade may disclose a primary defect in the calcium-dependent control of vascular smooth muscle.…”

“…8 - 10 In addition, diuresis and natriuresis are typically associated with the renal vasodilation induced by these drugs when administered to hypertensive subjects. 11 Furthermore, recent studies have shown that the renal vasculature of normotensive relatives of hypertensive patients is abnormally sensitive to the dilating effect of intrarenally infused diltiazem.…”

Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II.

“…One of the 189 (91-550) unique features of the increased vascular sensitivity characteristic of the hypertensive state is that it is not the same for all 8.4 (3-32)* stimuli (31). Thus, the increased cardiovascular responsiveness 13.3 to NA in essential hypertension can be normalized by potassium supplementation or calcium reentry blockade in contrast 16.0 (91-2)t to that to All (3,32). The pathophysiological mechanism un-20.8 (l2-58) § derlying that difference, however, remains to be elucidated.…”