Multiple factors contribute to acetylcholine-induced renal afferent arteriolar vasodilation during myogenic and norepinephrine- and KCl-induced vasoconstriction. Studies in the isolated perfused hydronephrotic kidney.
Acetylcholine (ACh) elicits vasodilation by releasing a number of endothelium-derived relaxing factors (EDRFs). We used the isolated perfused hydronephrotic rat kidney to examine the characteristics of ACh-induced vasodilation of renal afferent arterioles during different types of underlying vasoconstriction. Basal arteriolar tone was increased by either elevating perfusion pressure to 180 mm Hg (myogenic), administering 0.3 mumol/L norepinephrine (NE), or elevating medium potassium concentration to 30 mmol/L (KCl). ACh (10 mumol/L) completely reversed myogenic and NE-induced vasoconstriction and reversed KCl-induced vasoconstriction by 80 +/- 5%. However, whereas ACh produced a sustained vasodilation during KCl- and NE-induced vasoconstriction, only a transient reversal of myogenic vasoconstriction was observed, and myogenic tone recovered within 5 to 10 minutes. ACh-induced vasodilation of arterioles preconstricted with KCl was markedly inhibited by either indomethacin (100 mumol/L) or nitro-L-arginine (100 mumol/L) and was completely abolished by pretreatment with both inhibitors. In contrast, indomethacin and nitro-L-arginine had no effect on the transient response to ACh observed during pressure-induced vasoconstriction. In vessels preconstricted with NE, nitro-L-arginine converted the normally sustained response to ACh to a transient vasodilation, which was refractory to both nitric oxide synthase and cyclooxygenase inhibition. Since this component was not observed during KCl-induced vasoconstriction, it may reflect the actions of an, as yet unidentified, endothelium-derived hyperpolarizing factor (EDHF). Our findings thus suggest that prostanoids, nitric oxide, and EDHF all contribute to ACh-induced renal afferent arteriolar vasodilation and that the relative contributions of these individual EDRFs depends on the nature of the underlying renal vascular tone.
Hayashi
K
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Loutzenhiser
R
R
Epstein
M
M
Suzuki
H
H
Saruta
T
T
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology*; D001685:Biological Factors / Q000502:physiology*; D006869:Hydronephrosis / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000502:physiology
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D011189:Potassium Chloride; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin