Comparison of the effects of angiotensin II, losartan, and enalapril on baroreflex control of heart rate in conscious rabbits.
We compared the effects of angiotensin II (AII), enalapril, and losartan given by acute intravenous (i.v.) injection, on cardiac baroreflex sensitivity in two groups of conscious normotensive rabbits bred for high gain [> 5 beats/min/mm Hg] (group I) and low gain [< 4 beats/min/mm Hg] (group II) of the mean arterial blood pressure-heart rate (MAP/HR) relationship, respectively. Full sigmoid barocurves were produced in 62 rabbits by i.v. injection of phenylephrine (PE 1-15 micrograms/kg) and nitroglycerin (NTG 1-20 micrograms/kg) after pretreatment with saline or with AII, enalapril, or losartan. In group II, AII had a biphasic effect on baroreflex sensitivity; at 10 and 50 ng/kg/min, it increased the gain from 3.47 +/- 0.21 to 4.75 +/- 0.44 and 5.13 +/- 0.28 beats/min/mm Hg (p < 0.05 and p < 0.025, respectively), but had no effect at 100 ng/kg/min. BP increased in these rabbits by 11.5, 10, and 23 mm Hg after these three doses. In group I, AII 50 ng/kg/min increased BP by 8 mm Hg, (p < 0.05) and decreased gain from 6.13 +/- 0.32 to 4.75 +/- 0.44 beats/min/mm Hg (p < 0.01). Therefore, AII 50 ng/kg/min equalized baroreflex sensitivity in the two groups. In group II, both losartan (2.5 mg/kg) and enalapril (1 mg/kg) decreased BP by 8.6 +/- 1.0 1.0 and 10.2 +/- 2.1 mm Hg, (p < 0.01), respectively, and increased the gain by 1-2 beats/min/mm Hg; the drugs did not influence baroreflex sensitivity to any significant extent in group I.(ABSTRACT TRUNCATED AT 250 WORDS)
Weinstock
M
M
Department of Pharmacology, School of Pharmacy, Hebrew University Hadassah Medical Centre, Ein Kerem, Jerusalem, Israel.
Gorodetsky
E
E
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000235:genetics; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan