Pathophysiological significance of T-type Ca2+ channels: role of T-type Ca2+ channels in renal microcirculation.
Since conventional Ca(2+) antagonists, with predominant blockade of L-type voltage-dependent Ca(2+) channels, elicit preferential dilation of afferent arterioles, they might ostensibly aggravate glomerular hypertension. Recently, novel Ca(2+) antagonists, with inhibitory action on L-/T-type Ca(2+) channels, have been reported to dilate both afferent and efferent arterioles. The present review attempted to characterize the renal action of these Ca(2+) antagonists and evaluated the consequences following the treatment with these agents. In contrast to conventional Ca(2+) antagonists (e.g., nifedipine), novel antagonists (e.g., benidipine, efonidipine) potently dilated afferent and efferent arterioles; their action on efferent arterioles appeared to be mediated by the T-type Ca(2+) channel blockade, probably through the inhibition of the intracellular Ca(2+) release. The comparison of the anti-proteinuric action in subtotally nephrectomized rats showed that efonidipine exerted more prominent action than nifedipine. Furthermore, Ca(2+) antagonists with T-type Ca(2+) inhibitory action inhibited renin/aldosterone release and proinflammatory process. Finally, patients with chronic renal disease given a 48-week efonidipine treatment showed reduced proteinuria, and this effect was seen even when mean arterial blood pressure failed to become less than 100 mmHg. Collectively, T-type Ca(2+) channel blockade provides beneficial action in renal injury. Various mechanisms serve to protect against renal injury, including systemic/glomerular hemodynamic action and non-hemodynamic mechanisms.
Hayashi
Koichi
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. khayashi@sc.itc.keio.ac.jp
Wakino
Shu
S
Homma
Koichiro
K
Sugano
Naoki
N
Saruta
Takao
T
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D004095:Dihydropyridines / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000188:drug therapy; D008833:Microcirculation; D009596:Nitrophenols / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D012079:Renal Circulation / Q000502:physiology*; D015398:Signal Transduction
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D002118:Calcium