Endogenous angiotensin II enhances phenylephrine-induced tone in hypertensive rats.
Subthreshold concentrations of angiotensin II (Ang II) potentiate agonist-induced tone in a variety of blood vessels. We measured in vivo the mesenteric artery diameter and blood flow in 12-week-old normotensive Wistar-Kyoto (WKY) rats (n = 20) and spontaneously hypertensive rats (SHR, n = 20); systemic blood pressure was monitored continuously. Phenylephrine (10 mumol/L) superfused on the exteriorized mesentery reduced arterial diameter from 480 +/- 40 to 256 +/- 18 microns (P < .05) in WKY rats and from 562 +/- 26 to 273 +/- 7 microns (P < .05) in SHR, whereas blood flow was lowered by 77% in WKY rats and 76% in SHR (P < .05 in both strains). Topical superfusion of an angiotensin-converting enzyme inhibitor (perindoprilat, 10 and 100 mumol/L) attenuated the phenylephrine-induced decrease in diameter and blood flow in both strains (P < .05). The Ang II type 1 receptor blocker losartan (10 mumol/L) attenuated the phenylephrine-induced decrease in diameter and blood flow in both strains (P < .05). The relaxing effect of losartan was significantly accentuated by the addition of perindoprilat (10 mumol/L) to the superfusate (P < .05 in both strains). Systemic blood pressure was unaffected by the topical application of phenylephrine (10 mumol/L), perindoprilat (10 or 100 mumol/L), or losartan (10 mumol/L). We conclude that phenylephrine-induced tone impairment by angiotensin-converting enzyme inhibition and Ang II type 1 receptor blockade in vivo probably reflects the role of endogenous Ang II in the potentiation of the adrenergic response during the control of vascular tone. This role is identical in both normotensive and hypertensive rats.
Qiu
H Y
HY
Institut National de la Santé et de la Recherche Médicale (INSERM) U141, IFR Circulation, Université Paris VII, Hôpital Lariboisiere, France.
Henrion
D
D
Levy
B I
BI
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019808:Losartan; D008638:Mesenteric Arteries / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow; D013777:Tetrazoles / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D007211:Indoles; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; C053500:perindoprilat; D019808:Losartan