The first-line depressor agents for hypertensive patients with chronic kidney disease are the renin-angiotensin
system inhibitors because of their antiproteinuric and reno-protective effects. However, only one renin-angiotensin system
inhibitor often cannot achieve target blood pressure in patients with injured kidney. Thus, second-line antihypertensives
are required. Calcium channel blockers are frequently added on the renin-angiotensin system inhibitors in hypertensive
patients with chronic kidney disease. However, they do not always show reno-protective effects because of their
glomerular pressure-increasing action; Antihypetensive calcium channel blockers suppress L-type calcium channels,
which exist in glomerular afferent but not efferent arterioles, and their afferent arteriole-specific vasodilation causes
glomerular hypertension. The decrease in glomerular pressure due to their systemic hypotesive effect is counteracted by
the glomerular pressure-incresing action. However, L-/N-type calcium channel blockers inhibits norepinephrine release
from the sympathetic nerve terminal by blockade of N-type calcium channels, and dilate both afferent and efferent
arterioles, which were innervated sympathetically, resulting in decrease in glomerular pressure. Actually, we have
demonstrated that an L-/N-type calcium channel blocker cilnidipine decreased urinary protein more greatly than an L-type
calcium channel blocker amlodipine in the renin-angiotensin system inhibitor-treated patients with chronic kidney disease.
Thus, L-/N-type calcium channel blockers are one of suitable candidates for the second-line antihypertensives in the
renin-angiotensin system inhibitor-treated hypertensive patients with proteinuria.
N-type calcium channel, chronic kidney disease, afferent arteriole, glomerular pressure, sympathetic nervous
Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3- 1 Hongo, Bunkkyo-ku, Tokyo, 113-8655, Japan.