T-type Ca channel blockade as a determinant of kidney protection.
Voltage-dependent Ca channels are classified into several subtypes based on the isoform of their α1 subunits. Traditional Ca channels blockers (CCBs), including nifedipine and amlodipine, act predominantly on L-type Ca channels, whereas novel CCBs such as efonidipine, benidipine and azelnidipine inhibit both L-type and T-type Ca channels. Furthermore, cilnidipine blocks L-type and N-type Ca channels. These CCBs exert divergent actions on renal microvessels. L-type CCBs preferentially dilate afferent arterioles, whereas both L-/T-type and L-/N-type CCBs potently dilate afferent and efferent arterioles. The distinct actions of CCBs on the renal microcirculation are reflected by changes in glomerular capillary pressure and subsequent renal injury: L-type CCBs favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. The renal protective action of L-/T-type CCBs is also mediated by non-hemodynamic mechanisms, i.e., inhibition of the inflammatory process and inhibition of Rho kinase and aldosterone secretion. Finally, a growing body of evidence indicates that T-type CCBs offer more beneficial action on proteinuria and renal survival rate than L-type CCBs in patients with chronic kidney disease (CKD). Similarly, in CKD patients treated with renin-angiotensin blockers, add-on therapy with N-type CCBs is more potent in reducing proteinuria than that with L-type CCBs, although no difference is found in the subgroup with diabetic nephropathy. Thus, the strategy for hypertension treatment with CCBs has entered a new era: treatment selection depends not only on blood pressure control but also on the subtypes of CCBs.
Hayashi
Koichi
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. khayashi@sc.itc.keio.ac.jp
Homma
Koichiro
K
Wakino
Shu
S
Tokuyama
Hirobumi
H
Sugano
Naoki
N
Saruta
Takao
T
Itoh
Hiroshi
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D009596:Nitrophenols / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine