Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin.
Angiotensin (ANG) can produce a biphasic arterial pressure response, i.e., an increase followed by a decrease. Because ANG type 1 (AT1) receptors mediate the pressor response to ANG, we hypothesized that the opposing depressor action is mediated by the ANG type 2 (AT2) receptors. In thiobutabarbital (Inactin)-anesthetized rats bolus injections of angiotensin III (ANG III; 100, 300, and 1,000 ng/kg iv) produced peak increases in MAP at 20 s of 13.4 +/- 1.4, 20.1 +/- 2, and 27.5 +/- 2.8 mmHg and maximum decreases in pressure at 120 s of -6.3 +/- 1.5, -6.8 +/- 2.2, and -11.4 +/- 4.9 mmHg. During blockade of the AT1 receptors with DuP 753 (losartan, 10 mg/kg) the increases in MAP were eliminated (P < 0.01), whereas the depressor responses (-24.7 +/- 8, -32.8 +/- 9.3, and -42.0 +/- 10.0 mmHg) were significantly (P < 0.05) larger. In separate groups of rats, combined blockade of both AT1 and AT2 receptors eliminated all changes in MAP in response to ANG III, whereas blockade of AT2 receptors alone enhanced the pressor response to ANG III. During AT1 receptor blockade angiotensin II also caused consistent decreases in pressure, which were inhibited during combined blockade of AT1 and AT2 receptors. Therefore, we have demonstrated that the AT2 receptors mediate a depressor response to ANG.
Rhône Poulenc Rorer Central Research, Collegeville, Pennsylvania 19426-0107.
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Scheuer
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Perrone
D000804:Angiotensin II / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; D012504:Saralasin; D019808:Losartan