Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibition with captopril in the therapy of patients with severe primary hypertension.

Abstract

Nifedipine (10 mg qid) and captopril (25 mg qid) were tested alone and in combination in 14 patients suffering from severe primary hypertension. Each study period was of 1 week's duration. Circulatory response was evaluated through hourly pressure and pulse rate readings. The fall in pressure after oral nifedipine was maximal within 1 hr or less and was generally accompanied by palpitation and increase in pulse rate; with a six hourly dosing regimen the tendency of blood pressure to recover after each dose was interrupted by the next dose, so that values remained significantly reduced throughout the 24 hr, although pressure fluctuations were evident. Promptness of the antihypertensive action of captopril was similar, but the magnitude and the duration of the fall in pressure were less pronounced. When the converting-enzyme inhibitor was combined with the calcium-channel blocker, pressure fluctuations were not abolished, but the antihypertensive response was definitely enhanced, so that normal blood pressure was maintained for several hours during the day. Additional positive effects of captopril were mitigation of the heart rate reaction and prevention of the ankle pitting or edema elicited by nifedipine. A balance in arteriolar and venular dilatation promoted by captopril is the suggested mechanism for these effects. With the two-drug combination the function of the left ventricle was not reduced and possibly improved; blood urea nitrogen and serum electrolyte and creatinine concentration were not affected. Plasma renin activity increased with captopril and reverted toward baseline with the addition of nifedipine, suggesting an interference of the calcium-channel blocker with the release of renin. Circulation 70, No. 2, 279-284, 1984. CALCIUM ANTAGONISTS block transmembrane Ca supply and reduce the contractile vascular muscle activity in a dose-related manner. However, the higher the wall tension is elevated above normal, the more relaxation is induced by a given concentration of Ca antagonist.' Because of this, the use of these compounds has been proposed in the management of hypertensive crises2 as well as in the treatment of essential hypertension.3 The hypotensive response to oral nifedipine is prompt, and a dosing regimen every 6 hr significantly lowers blood pressure over the 24 hr, although fluctuations are recorded owing to the rate of decay of the vasodilating effect.4 The reaction of pulse rate at the nadir of the hypotensive response to each

Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

“…These findings are in agreement with previous observations based on spontaneously reported side effects in clinical trials [8][9][10][11] and confirm and extend those of Weir et al, 22 who also used the water displacement technique to evaluate the effects of benazepril on the lower extremity oedema because of amlodipine.…”

“…In this study, the addition of benazepril to amlodipine provided greater BP reduction than either drug alone, which confirms previous observations. [6][7][8][9][10][11] In conclusion, the results of this study indicate that in patients with mild to moderate essential hypertension the addition of the ACE-I benazepril to the dihydropyridine Ca-antagonist amlodipine attenuated lower extremity oedema and provided better BP control, which strengthens the rationale to use an ACE-I/Ca-antagonist combination in the treatment of hypertension. Effect of benazepril -amlodipine combination on ankle oedema…”

“…6,7 In particular, the ACE-I/Ca antagonist combination has been shown to reduce the incidence of the most common side effect of dihydropyridine Ca-antagonists, ankle oedema. [8][9][10][11] Although the precise mechanisms causing the Ca-antagonist-induced oedema are still not completely understood, the most likely reason appears to be an increase in capillary hydrostatic pressure with consequent transcapillary fluid loss that results from a relatively more pronounced vasodilation in precapillary than postcapillary resistance vessels. [12][13][14] It has also been suggested that the Ca-antagonist-related oedema could be partly ascribed to interference by these drugs with the local vascular control (probably the myogenic component) that operates to protect dependent vascular regions from increased fluid filtration, 15,16 whereas sodium retention and activation of the renin-angiotensin system seem to play a minor role.…”

Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

“…These findings are similar to previous observations with the ACE-I/CCB combination, both based on spontaneously reported side effects in clinical trials [9][10][11][12] and also on the use of the water displacement technique. 13,14 The mechanisms by Valsartan-amlodipine combination and ankle oedema R Fogari et al which ARB may attenuate the CCB-induced oedema are not clear but possibly resemble those hypothesized for ACE-I.…”

“…6 By contrast, adding an angiotensin-converting enzyme inhibitor (ACE-I) to the treatment with a CCB has been shown to reduce the incidence and the entity of ankle oedema. [9][10][11][12][13] The mechanisms by which ACE-I attenuate the CCBinduced oedema are not clear, but their ability to dilate venous capacitance vessels seems to play a major role by normalizing intracapillary pressure and reducing fluid exudation from the intracapillary space into the interstitium. 6,14 Whether this ability is peculiar of ACE-I or extends to the other drugs interfering with the renin-angiotensin-aldosterone system (RAAS), that is the angiotensin receptor blockers (ARB), remains to be established.…”