[Interaction between SR 47436, a new angiotensin II antagonist and sympathetic nervous system in pithed SHR rats].
In vivo studies have previously shown that exogenous angiotensin II (AII) reinforces sympathetic nervous system activity. Conversely, non selective inhibition of endogenous AII by angiotensin I converting enzyme inhibitors (ACEIs) results in sympathoinhibitory effects. The aim of the present study was to examine the influence of selective inhibition of endogenous AII by SR 47436, a non peptide AT1-receptor antagonist, on the sympathetic nervous system. Cardiac, systemic and regional vascular (kidney, mesentery, hindlimb) responses to selective alpha 1- and alpha 2-adrenoceptor agonists and to electrical stimulation of the spinal cord were investigated in the pithed spontaneously hypertensive rat (SHR). Male adults SHRs were orally treated by SR 47436 (10 mg/kg/day for 8 days) or by distilled water. Two hours later, they were anesthetized with pentobarbital (50 mg/kg, i.p.), pithed and artificially ventilated. Blood pressure, heart rate, cardiac output and regional (kidney, mesentery and hindlimb) blood flows (pulsed Doppler technique) were measured. Corresponding vascular resistances were calculated. Three hours after SR 47436--at the time of the drug's maximal effects--or distilled water administration, cardiac, systemic pressor and regional vasoconstrictor responses (a) to increasing i.v. doses of AII, (b) to increasing frequencies of electrical stimulation of the spinal cord, and (c) to increasing i.v. doses of cirazoline, a selective alpha 1-adrenoceptor agonist, and of UK-14,304, a selective alpha 2-adrenoceptor agonist, were investigated. AII systemic pressor, regional vasoconstrictor and tachycardic responses were completely abolished by SR 47436. SR 47436 significantly reduced the systemic pressor responses elicited by spinal cord stimulation, cirazoline and UK-14,304.(ABSTRACT TRUNCATED AT 250 WORDS)
Moreau
N
N
Département de pharmacologie, faculté de médecine Paris-Sud. Le Kremlin-Bicêtre.
Richer
C
C
Vincent
M P
MP
Giudicelli
J F
JF
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003655:Decerebrate State; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000502:physiology; D000077405:Irbesartan; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D000077405:Irbesartan
Interaction entre le SR 47436, un nouvel antagoniste de l'angiotensin II, et le système sympathique chez le SHR amyélé.