Effects of losartan (DuP753) and enalaprilat on the mean arterial pressure response to phenylephrine.
BACKGROUND
We have found that low-dose infusion of angiotensin II (Ang II) selectively potentiates the mean arterial pressure (MAP) response to phenylephrine in pentobarbital-anesthetized rabbits.


OBJECTIVE
To examine whether endogenous Ang II levels in normotensive rabbits maintained on a normal-salt diet exert a potentiating effect on the MAP response to phenylephrine.


METHODS
We compared the effects of enalaprilat (0.3 mg/kg per min for 5 min bolus, 1 mg/kg per h infusion), losartan (DuP753; 4 mg/kg bolus, 2 mg/kg per h infusion) and vehicle administration on the MAP response to infusions of phenylephrine that were increased incrementally (2.5, 5 and 10 micrograms/kg per min).


RESULTS
Enalaprilat decreased MAP significantly, whereas no maintained change was observed with losartan or vehicle. Phenylephrine infusions elevated MAP significantly and dose-dependently in all of the rabbits studied, but this effect was attenuated significantly in the rabbits given losartan compared with in those given vehicle or enalaprilat. The heart rate responses were not significantly different among the three groups.


CONCLUSIONS
We conclude that inhibition of the renin-angiotensin system at two distinct sites results in different MAP responses to phenylephrine infusion.
Department of Pharmacology, Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877.
J B
JB
Madwed
R J
RJ
Winquist
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D019808:Losartan; D010656:Phenylephrine / Q000494:pharmacology*; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; D015773:Enalaprilat; D019808:Losartan