Involvement of angiotensin receptor subtypes in osmotically induced release of vasopressin.
We have previously shown that AT1 and AT2 angiotensin II (Ang II) receptors mediate the release of arginine vasopressin (AVP) to central injections of Ang II. In this study we have tested the hypothesis that Ang II, acting at AT1 and AT2 receptors in the brain, is involved in mediating osmotically stimulated AVP release. Adult Sprague-Dawley rats were fitted with intraventricular (i.v.t.) cannulas and catheters in the carotid artery and the femoral vein. Intraventricular injections of Ang II receptor antagonists specific to different subtypes of the receptor (AT1 and AT2) were given before a 30 min infusion of hypertonic (2.5 M) saline. Arterial blood samples were collected 5 min before and at two time points after (+15 min and +30 min) beginning the saline infusion. We found that both losartan (AT1 specific) and CGP42112A (AT2 specific) significantly reduced osmotically induced release of AVP. PD123319 (AT2 specific) had no effect of osmotically stimulated AVP release. A combined treatment of losartan + PD123319 was no more effective than losartan in blocking the AVP response. Since losartan was the most rapid and effective antagonist of osmotically stimulated AVP release, we conclude that AT1 receptors are directly involved in the response. However, but since CGP42112A was also an effective antagonist and since, AT2 receptors are located at sites distant from the hypothalamus, such as the locus ceruleus, they may also contribute to this response. We conclude that brain Ang II receptors are involved in osmotically stimulated AVP release.
Hogarty
D C
DC
Department of Physiology, University of Florida, Gainesville 32610.
Tran
D N
DN
Phillips
M I
MI
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D009994:Osmolar Concentration; D011725:Pyridines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D011945:Receptors, Angiotensin; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; D001127:Arginine Vasopressin; C060894:CGP 42112A; C073402:PD 123319; D019808:Losartan