Acute and Chronic Effect of Nifedipine in Primary Aldosteronism

Abstract

Since calcium entry blocker drugs can interfere with aldosterone secretion in vitro, a similar effect in vivo, in man, has been suggested and partially confirmed. The data available in primary aldosteronism are more controversial. Therefore, we have studied the acute and chronic effect of nifedipine in 7 patients with idiopathic hyperaldosteronism (IHA) and 8 with aldosterone producing adenoma (APA). On 2 different days, 10 mg of nifedipine or placebo were given sublingually to the patients and blood pressure and heart rate were recorded every 5 min. for 60 min. Plasma aldosterone, cortisol, PRA and serum K+ were measured at 0, 30 and 60 min. 5 patients with IHA and 6 with APA received nifedipine 20 mg per os bid for 3 months; the same parameters were evaluated on days 0, 30, 60 and 90; urinary aldosterone was measured on days 0, 30, 60 and 90. BP decreased in both groups both after acute and chronic administration of nifedipine. Plasma aldosterone showed a similar trend either after acute nifedipine or placebo; however, during chronic treatment it was slightly decreased in IHA patients. Cortisol, PRA, urinary aldosterone and K+ remained unchanged. In conclusion, nifedipine is an effective antihypertensive agent also in primary aldosteronism; its aldosterone inhibiting properties are minimal and seem to be present only during long-term therapy in IHA.

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

“…In the human adrenal cortex, CACNA1D transcripts are the most abundant Ca 2+ channel subunits (Scholl et al, 2013), suggesting that Ca V 1.3 channels are also important for regulation of physiologic aldosterone secretion. Despite this important role of LTCCs, CCBs lower blood pressure but do not effectively lower plasma aldosterone levels in most patients with primary hyperaldosteronism (Stimpel et al, 1988;Carpenè et al, 1989). This may be explained by the contribution of other Ca 2+ channels to aldosterone secretion, as recently reported for T-type channels in humans (Scholl et al, 2015) and rodents .…”

Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism

“…(1985) have shown a roughly 50% reduction in PAC in 10 patients with Conn's syndrome, five with APA and five with IHA, who received 40 mg nifedipine for 1 day. In a long‐term experiment Carpene et al . (1989) showed that over a treatment period of 90 days with 20 mg nifedipine per day, plasma aldosterone levels remained unchanged in six APA patients and were only minimally lower in five IHA patients.…”

“…Nadler et al (1985) have shown a roughly 50% reduction in PAC in 10 patients with Conn's syndrome, five with APA and five with IHA, who received 40 mg nifedipine for 1 day. In a long-term experiment Carpene et al (1989) showed that over a treatment period of 90 days with 20 mg nifedipine per day, plasma aldosterone levels remained unchanged in six APA patients and were only minimally lower in five IHA patients. Gallay et al (2001) reported that SAC remained high in six patients with PA on long-term calcium channel blocker medication and did not lead to false-negative results of the ARR screening test.…”

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

“…Apart from avoiding potassiumwasting diuretics (other than in occasional patients with reduced glomerular function who are prone to hyperkalemia on aldosterone antagonists) because of the propensity to induce or worsen hypokalemia, there is little evidence to favor one class of agents over another in this situation. Both ACE inhibitors (215,309) and calcium channel antagonists (75,237,358) have been shown to lower blood pressure in patients with PA. Although circulating levels of renin and ANG II in PA are suppressed, and hence the capability for ACE inhibitors to lower blood pressure would seem to be limited, it is possible that the effectiveness of these agents results from blockade of the tissue renin-angiotensin system (which is not suppressed in PA).…”

“…Furthermore, circulating renin levels may become unsuppressed in patients receiving sufficient doses of aldosterone antagonist agents, thereby potentially increasing the efficacy of medications (like ACE inhibitors and ARBs) which block the renin-angiotensin system. Synthesis of aldosterone in ZG cells is dependent on rises in intracellular calcium, and falls in aldosterone levels induced by calcium channel blockers in patients with PA have been reported (75,358,541). However, it is unclear whether this effect is sufficient to lower blood pressure to a significantly greater degree than by other, less-specific actions of calcium channel blockade.…”