Central sympathoinhibitory effects of calcium channel blockers

Abstract

It is generally assumed that the arterial vasodilation induced by inhibition of Ca(2+) influx into vascular smooth muscle cells represents the main mechanism for the hypotensive effect of dihydropyridine calcium channel blockers. Increases in sympathetic tone have been related to activation of the arterial baroreflex by rapid lowering of blood pressure. This review highlights new findings in two areas. First, in animal studies, direct central administration of dihydropyridines such as nifedipine or amlodipine lowers sympathetic nerve activity and thereby blood pressure. Peripheral administration of nifedipine or amlodipine at low rates appears to result in gradual accumulation of drug in the central nervous system, and also causes lowering of sympathetic nerve activity and thereby lowering of blood pressure (rather than by arterial vasodilation). Second, in hypertensive humans treated with long-acting dihydropyridines and presumably little activation of the arterial baroreflex, some studies have demonstrated lowering of sympathetic activity (as assessed by plasma norepinephrine), but others reported increases (as assessed by plasma norepinephrine or microneurography). This sympathoexcitatory response may be due to activation of the renin-angiotensin system, particularly at higher doses.

Cigarette Smoking Augments Sympathetic Nerve Activity in Patients With Coronary Heart Disease

“…45,46) It has also been shown that baroreflex sensitivity was increased significantly by chronic treatment with a Ca antagonist in patients with hypertension 47) and some Ca antagonists inhibited sympathetic nerve activity. 48,49) Therefore, in patients with stable effort angina and with impaired BRS, the same mechanisms might be observed with an ACE inhibitor or a Ca antagonist. These medications might alter the effect of cigarette smoking.…”

Effects of a New Calcium Channel Blocker, Azelnidipine, on Systemic Hemodynamics and Renal Sympathetic Nerve Activity in Spontaneously Hypertensive Rats

“…Dihydropyridine CCBs have been shown to cause reflex sympathetic stimulation and tachycardia in association with a decrease in blood pressure (4,21), and this increased cardiac workload has been considered responsible for their limited preventive effects against cardiac complications (2,3). However, recent clinical studies indicated that tachycardia was not associated with the antihypertensive effects of azelnidipine, a new lipophilic dihydropyridine CCB (13,15).…”

“…However, it has been revealed that nifedipine, a short-acting dihydropyridine CCB, increases the risks of ischemic heart disease (2,3), a phenomenon that is thought to be mainly related to its reflex responses, i.e., activation of the sympathetic nervous system and tachycardia after rapid lowering of blood pressure (4). Therefore, the use of long-acting dihydropyridine CCBs is generally recommended in hypertensive patients (5,6).…”

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

“…Atorvastatin also reduces oxidative stress in the RVLM of SHRSP (62,63,64). With regard to the central sympathoinhibitory effects of calcium channel blockers, lipophilic dihidropyridine calcium channel blockers, such as nifedipine, nisoldipine, and amlodipine, readily cross the blood-brain barrier, thereby presumably blocking brain L-type Ca 2ϩ channels leading to central sympathoinhibition (73). It is generally considered that an arterial baroreflex-mediated increase in sympathetic activity is responsible for the unfavorable effects of short-and strong-acting dihydropyridine calcium channel blockers; therefore, the intrinsic sympathoinhibitory effects of calcium channel blockers have been ignored.…”