Acute hemodynamic effects of combined inhibition of neutral endopeptidase and angiotensin converting enzyme in spontaneously hypertensive rats.
Neutral endopeptidase inhibitors (NEPI) potentiate the hypotensive effect of converting enzyme inhibitors (CEI) in conscious spontaneously hypertensive rats (SHR) but the mechanism of this potentiation remains unknown. The present study assesses the hemodynamic effects of a CEI (enalaprilat 1 mg/kg; n = 9), a NEPI (retrothiorphan 25 mg/kg + 25 mg/kg/h; n = 9) and the combination (CEI+NEPI; n = 9) versus a control group (n = 9) in anesthetized spontaneously hypertensive rats. CEI alone induced a significant hypotensive effect due to a decrease (-35.1%) in total peripheral resistance (TPR), with no significant increase in cardiac output (CO). NEPI alone had a slight hypotensive effect due to a small decrease in CO. CEI+NEPI decreased the mean arterial pressure to the same extent (-26.7%) as the CEI-induced hypotensive effect, decreased TPR (-44.4%) and induced an increase in CO (+38.2%) with an increase in heart rate. In summary, NEPI combined with CEI induces large decreases in blood pressure and in TPR which do not significantly differ from the CEI-induced effects. It also induces increases in heart rate and in cardiac output in anesthetized SHR.
Pham
I
I
INSERM U 367, Paris, France.
Lévy
B
B
Fournié-Zaluski
M C
MC
Poitevin
P
P
Roques
B P
BP
Michel
J B
JB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D015773:Enalaprilat / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy; D007700:Kinetics; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D015244:Thiorphan / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; C072559:retrothiorphan; D015244:Thiorphan; D015260:Neprilysin; D015773:Enalaprilat