Cardiovascular consequences of microinjection of vasopressin and angiotensin II in the area postrema.
Microinjection of angiotensin II (ANG II) into the area postrema (AP) of urethan-anesthetized male Sprague-Dawley rats elicited statistically significant increases in mean arterial blood pressure at doses ranging from 10 pg to 500 ng (10 pg, mean +/- SE, 10.8 +/- 1.1 mmHg, P < 0.001; 250 ng, 15.2 +/- 2.6 mmHg, P < 0.001). Heart rate was also significantly increased at doses > 10 pg, although these increases were not dose dependent. Systemic administration of losartan (Dup-753), an AT1 antagonist, was able to significantly reduce the pressor response to 250 ng ANG (post-losartan: 81.9 +/- 9.5% reduction in blood pressure response, P < 0.0001), whereas PD123319, an AT2 antagonist, was without significant effect (P > 0.1). Microinjection of vasopressin (VP) (10 pg-500 ng) into the AP also resulted in statistically significant increases in blood pressure at doses ranging from 10 to 100 pg (10 pg, 7.0 +/- 1.5 mmHg, P < 0.05) and 100-500 ng (250 ng, 12.2 +/- 1.8 mmHg, P < 0.0001). Small but significant changes in heart rate were observed only at 100 pg and 100 ng. Systemic administration of a V1 antagonist significantly attenuated the increases in blood pressure in response to 50, 100, and 250 ng VP (250 ng, post-V1 antagonist: 66.4 +/- 8.6% reduction in blood pressure response, P < 0.001), whereas [desamino,D-Arg8]vasopressin (DDAVP), a V2 agonist, had a depressor effect when microinjected directly into the AP (250 ng, -9.9 +/- 1.6 mmHg, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Lowes
V L
VL
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
McLean
L E
LE
Kasting
N W
NW
Ferguson
A V
AV
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014667:Vasopressins; D000804:Angiotensin II; D019808:Losartan