title: Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.
abstract: To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29+/-3 (n = 8, P < 0.01) and 27+/-3% (n = 8, P < 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65+/-9% (P < 0.01). In the second group, the addition of N-ethylmaleimide (10 microM), a Gi/Go protein antagonist, abolished AngII- induced EA (n = 6) but not AA constriction (n = 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 microM), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII (n = 6 for each). In the fourth group, thapsigargin (1 microM) prevented AngII-induced AA constriction (n = 8) and attenuated EA constriction (8+/-2% decrease in EA diameter at 0.3 nM AngII, n = 8, P < 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry.
authors.affiliation: Shinjuku Suimei Clinic, Shinjuku, Tokyo, 160, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Nagahama
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009401:Nephrosis; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D048448:Phenylcarbamates; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002219:Carbamates; D048448:Phenylcarbamates; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D000804:Angiotensin II; D019284:Thapsigargin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D009543:Nifedipine; D005033:Ethylmaleimide; D002118:Calcium