Cardiovascular effects after the intracerebroventricular administration of peptide and nonpeptide angiotensin antagonists in Dahl salt-sensitive rats.
Cardiovascular responses after the central blockade of the brain angiotensin system with peptide or nonpeptide angiotensin II analogs in conscious, freely moving hypertensive Dahl salt-sensitive (DS/JR) rats were measured. Four-week-old animals were maintained on an 8% salt diet until experimentation at 7 weeks of age. At the time of experimentation, mean arterial pressures were 176 +/- 6 mm Hg. The i.c.v. administration of 20 micrograms of the peptide analog sarcosine1, threonine8-angiotensin II (sarthran) resulted in a significant bradycardic response (approximately 17% decrease in H.R. peaking at 8 min after injection) without a significant change in blood pressure. Central administration of the AT1 antagonist losartan (10 micrograms) or of the AT2 antagonist PD 123319 (10 micrograms) was without effect. The peptide and nonpeptide analogs differed in their ability to inhibit central angiotensin II (10 ng)-induced pressor and dipsogenic responses. PD 123319 (10 micrograms) had no effect on the pressor and dipsogenic responses, whereas losartan (10 micrograms) and sarthran (20 micrograms) inhibited both responses for 85 +/- 17 and 29 +/- 3 min, respectively. The effect of preblocking either the AT1 or the AT2 receptors on the sarthran-induced bradycardia was also determined. Preblocking with either losartan (10 micrograms) or PD 123319 (10 micrograms) inhibited the bradycardic response by approximately 45%, which suggests that both receptor subtypes are involved in the central cardiovascular responses in the DS/JR rat and that, because it was attenuated by pure antagonists, the response to sarthran may be mediated by its agonist actions.(ABSTRACT TRUNCATED AT 250 WORDS)
Lark
L A
LA
Department of Cell and Structural Biology, University of Illinois, Urbana, USA.
Wappel
S M
SM
Weyhenmeyer
J A
JA
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D019808:Losartan