Angiotensin AT(2) receptors mediate vasodepressor response to footshock in rats. Role of kinins, nitric oxide and prostaglandins.
Footshocks increased mean arterial pressure and heart rate. Systemic administration of losartan, a specific angiotensin AT(1) receptor antagonist, not only inhibited the pressor response to footshocks, but also resulted in vasodepression. Administration of 1-[[4-(dimethylamino)3-methylphenyl]methyl]-5 (diphenylacetyl)-4,5,6, 7-tetrahydro-1H imidazol (4,5-c] pyridine-6-carboxilic acid, ditrifluoro acetatemonohydrate (PD 123319), a specific angiotensin AT(2) receptor antagonist, did not alter the hemodynamic response to footshocks. Simultaneous blockade of angiotensin AT(1) and AT(2) receptors by combined administration of losartan and PD 123319, eliminated the vasodepressor response to footshocks unmasked in losartan-pretreated rats. Saralasin, a non-specific angiotensin receptor antagonist, abolished the cardiovascular response to footshocks similarly like the losartan+PD 123319 treatment. Our data suggest that the vasodepressor response to footshocks in the presence of an angiotensin AT(1) receptor antagonist is triggered by activation of angiotensin AT(2) receptors. We studied the role of kinins, nitric oxide and prostaglandins in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan-treated rats was blunted by icatibant (HOE 140), N(G)-nitro-L-arginine-methyl ester (L-NAME) or indomethacin, indicating that kinins, nitric oxide and prostaglandins appear to be involved in the pressure response to footshocks during angiotensin AT(1) receptor blockade.
Israel
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School of Pharmacy, Universidad Central de Venezuela and Schools of Medicine, Apartado Postal 50176, Sabana Grande 1050, Caracas, Venezuela. astern88@hotmail.com
Cierco
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Sosa
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D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004597:Electroshock; D006339:Heart Rate; D007093:Imidazoles / Q000494:pharmacology; D007705:Kinins / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*
D007093:Imidazoles; D007705:Kinins; D011453:Prostaglandins; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C073402:PD 123319; D009569:Nitric Oxide; C065679:icatibant; D019808:Losartan; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester