Ca2+ channel subtypes and pharmacology in the kidney.
A large body of evidence has accrued indicating that voltage-gated Ca(2+) channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca(2+) channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca(2+) channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca(2+) channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca(2+) channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca(2+) channels and elicit vasodilation of afferent and efferent arterioles, which suggests the presence of T-type Ca(2+) channels in both arterioles and the distinct impact on intraglomerular pressure. Recently, aldosterone has been established as an aggravating factor in kidney disease, and T-type Ca(2+) channels mediate aldosterone release as well as its effect on renal efferent arteriolar tone. Furthermore, T-type CCBs are reported to exert inhibitory action on inflammatory process and renin secretion. Similarly, N-type Ca(2+) channels are present in nerve terminals, and the inhibition of neurotransmitter release by N-type CCBs (eg, cilnidipine) elicits dilation of afferent and efferent arterioles and reduces glomerular pressure. Collectively, the kidney is endowed with a variety of Ca(2+) channel subtypes, and the inhibition of these channels by their specific CCBs leads to variable impact on renal microcirculation. Furthermore, multifaceted activity of CCBs on T- and N-type Ca(2+) channels may offer additive benefits through nonhemodynamic mechanisms in the progression of chronic kidney disease.
Hayashi
Koichi
K
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. khayashi@sc.itc.keio.ac.jp
Wakino
Shu
S
Sugano
Naoki
N
Ozawa
Yuri
Y
Homma
Koichiro
K
Saruta
Takao
T
D000450:Aldosterone / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D006869:Hydronephrosis / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D000450:Aldosterone; D012083:Renin