Brain AT(2) receptor mediate vasodepressor response to footshocks: role of kinins and nitric oxide.
In the present study the role of brain AT(2) receptor in the cardiovascular response to stress was investigated in conscious rats. Footshock-stress increased mean arterial pressure (MAP) and heart rate (p < 0.0001). Intracerebroventricular (i.c.v.) administration of losartan (100 microg/5 microl), a specific angiotensin AT(1) receptor antagonist, not only attenuated the pressor response to footshocks, but also resulted in a consistent vasodepressor response (-10 mmHg, p < 0.02). Meanwhile, heart rate response was not altered. Given alone, PD 123319 (3 microg/5 microl, i.c.v.), a specific angiotensin AT(2) receptor antagonist, did not alter the hemodynamic response to footshocks. However, simultaneous block of brain AT(1) and AT(2) receptors by combined administration of losartan and PD 12319, eliminated the vasodepressor response unmasked after footshocks in rats i.c.v.-pretreated with losartan alone. In addition, we studied the role of brain kinins and nitric oxide (NO) in the vasodepressor response observed after footshocks in losartan i.c.v.-treated rats. Intracerebroventricular administration of icatibant (20 pmol/5 microl), a selective B(2) receptor antagonist, or N(G)-nitro-L-arginine methyl ester (100 microg/5 microl), a selective NO-synthase inhibitor, abolished the vasodepressor response to footshocks in losartan-treated rats. Our data suggest that the vasodepressor response to footshocks in the presence of AT(1) antagonist is triggered by activation of AT(2) receptor. Brain NO and kinins appear to contribute in this effect.
Israel
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School of Pharmacy, Universidad Central de Venezuela, Caracas Schools of Medicine, Caracas, Venezuela. astern88@hotmail.com
Sosa
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Gutierez
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D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D001921:Brain / Q000378:metabolism*; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005121:Extremities; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019335:Nitroarginine; C065679:icatibant; D019001:Nitric Oxide Synthase; D019808:Losartan; D001920:Bradykinin