Depressor effect of blocking angiotensin subtype 1 receptors in anterior hypothalamus.
Previous studies have shown that the anterior hypothalamic area participates in the centrally mediated pressor response to exogenous angiotensin II. The current study was designed to test the hypothesis that endogenous anterior hypothalamic angiotensin II plays a significant role in blood pressure control. Type 1 angiotensin II receptors in the anterior hypothalamic area were blocked by local microinjection of DuP 753 (2-n-butyl-4-chloro-5-(hydroxymethyl)-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]imidazole, potassium salt), a highly selective nonpeptide antagonist. DuP 753 (20 or 40 micrograms; in 100 nl artificial cerebrospinal fluid) or vehicle alone was microinjected into the anterior hypothalamic area of conscious NaCl-sensitive spontaneously hypertensive rats and Wistar-Kyoto controls. DuP 753 caused significant dose-related decreases in mean arterial pressure (maximal decrease, 22.5 +/- 1.8 mm Hg) with unchanged heart rate in NaCl-sensitive spontaneously hypertensive rats but effected no change in Wistar-Kyoto rats. Injections of equal volumes of artificial cerebrospinal fluid into the anterior hypothalamic area had no effect in either strain. Further, microinjection of DuP 753 into the posterior hypothalamic area produced no significant effect on blood pressure or heart rate in NaCl-sensitive spontaneously hypertensive rats. Microinjection into the anterior hypothalamic area of the selective type 2 angiotensin II receptor antagonist PD 123319 did not affect blood pressure or heart rate in NaCl-sensitive spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
R H
RH
Department of Medicine, University of Alabama, Birmingham 35294.
Jin
H
H
Wyss
J M
JM
Oparil
S
S
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007032:Hypothalamus, Anterior / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008845:Microinjections; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000145:classification / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan