Mechanosensitive cation channels mediate afferent arteriolar myogenic constriction in the isolated rat kidney.
1. In order to assess ionic mechanisms mediating renal afferent arteriolar myogenic constriction, experiments were performed using isolated perfused hydronephrotic rat kidneys. 2. Increasing pressure progressively constricted the afferent arteriole (-0.26 +/- 0.02% mmHg-1, n = 21, r = 0.97). Gadolinium (10 microM), a mechanosensitive cation channel blocker, abolished this myogenic constriction. However, high potassium media (30 mM) constricted the afferent arteriole in the presence of gadolinium. 3. Lowering extracellular sodium concentration gradually attenuated afferent arteriolar myogenic constriction. In the perfusate containing 50 mM sodium, the myogenic response was arrested. 4. Afferent arteriolar myogenic constriction was prevented in calcium-free perfusate or by the L-type calcium channel blocker diltiazem (10 microM). 5. Our present findings provide evidence that increasing pressure gates mechanosensitive cation channels on the afferent arteriole, thereby eliciting membrane depolarization and activating voltage-dependent calcium channels.
Department of Medicine, Saitama Medical College, Iruma, Saitama 340-03, Japan.
T
T
Takenaka
H
H
Suzuki
H
H
Okada
K
K
Hayashi
Y
Y
Kanno
T
T
Saruta
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D004110:Diltiazem / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D005682:Gadolinium; D004110:Diltiazem; D011188:Potassium