L-/N-type calcium channel blockers and proteinuria.
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.
Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3- 1 Hongo, Bunkkyo-ku, Tokyo, 113-8655, Japan. katsua-tky@umin.ac.jp.
Katsuyuki
K
Ando
D000419:Albuminuria / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D019317:Evidence-Based Medicine; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type