New Generation Calcium Channel Blockers in Hypertensive Treatment

Abstract

During a couple of decades, a number of antihypertensive drugs have been developed, and the choice of hypertension treatment has been expanded. Among antihypertensive drugs, calcium channel blockers, which inhibit L-type voltage-gated calcium channels, are potent vasodilators, and have been used as a first- or second-line drug. Dihydropyridine-class calcium channel blockers are categorized into three generations according to the length of activity, and long-acting calcium channel blockers cause less activation of sympathetic nervous system, and are reported to offer beneficial action compared with short-action agents. Furthermore, novel types of calcium channel blockers have been developed that possess the blocking action on other calcium channel subtypes (T- and N-type), and exert agent-specific action apart from their class effects, such as the effects on heart rate and renin/aldosterone release. These additional benefits conferred by T/N-type calcium channel blockade are anticipated to provide organ protective actions in the treatment of hypertension, in addition to the blood pressure-lowering effect of L-type calcium channel blockade. In conclusion, novel calcium channel blockers with sustained activity and T/N-type calcium channel blocking action could provide more beneficial effects than classical blockers, and may expand the clinical utility of these agents.

Fig. 1

Divergent vasodilator action of calcium antagonists on efferent arterioles. Based on the relative activity on efferent vs. afferent arterioles, calcium antagonists are classified into 3 groups. The first group of calcium antagonists (e.g., nifedipine) elicits predominant vasodilation of afferent arterioles, with modest action on efferent and efferent arterioles. The second group (e.g., nilvadipine) produces both afferent and efferent arteriolar vasodilation, although the efferent arteriolar vasodilation is less than that on the afferent arteriole. The third group of calcium antagonists (e.g., efonidipine) potently relaxes both afferent and efferent arterioles, with nearly the same activity on these vessels. *p < 0.05 vs. baseline. ? = Not examined. From Hayashi et al. [106] with modifications.

Fig. 2

Role of systemic blood pressure in the development of proteinuria in patients with proteinuria > 1 g/day treated with angiotensin converting enzyme inhibitors and efonidipine. ACE-I = angiotensin converting enzyme inhibitors; MAP = mean arterial pressure. From Hayashi et al. [109] with modifications.