Perindopril, a new converting enzyme inhibitor: systemic and regional hemodynamics and sympathoinhibitory effects in spontaneously hypertensive rats.
The effects of a new converting enzyme inhibitor, perindopril (5 mg/kg p.o. q.d. for 8 days), on systemic and regional hemodynamics, as well as its interferences with the sympathetic nervous system at the cardiovascular level, were investigated in nonbinephrectomized and in binephrectomized spontaneously hypertensive rats (SHRs). Perindopril abolished plasma converting enzyme activity and lowered arterial blood pressure (BP) without affecting heart rate. Cardiac index (microspheres) was not drug affected; thus, the reduction in BP was due to a decrease in total peripheral resistance which was shown to be homogenous, since all investigated vascular resistances were reduced to the same extent. In nonbinephrectomized, pithed SHRs, perindopril decreased BP and renal and hindlimb vascular resistances (pulsed Doppler). In addition, perindopril exerted a sympathoinhibitory effect as evidenced by (a) a reduction in the systemic vasopressor and regional vasoconstrictor responses to the alpha 1-adrenoceptor agonist, cirazoline, and especially to the alpha 2-adrenoceptor agonist UK 14.304; and (b) a decrease in the systemic pressor and in the hindlimb vasoconstrictor responses to spinal cord stimulation. In binephrectomized, pithed SHRs, perindopril no longer decreased BP; however, whereas its sympathoinhibitory effect versus alpha-adrenoceptor agonists was abolished, that versus spinal cord stimulation persisted. These results indicate that (a) perindopril lowers BP in SHRs by a renal-dependent mechanism; (b) perindopril exerts in SHRs a sympathoinhibitory effect versus alpha-adrenoceptor agonists and spinal cord stimulation; (c) the sympathoinhibitory effect of perindopril versus alpha-adrenoceptor agonists is postjunctional and kidney dependent; and (d) the sympathoinhibitory effect of perindopril versus spinal cord stimulation is possibly prejunctional in its mechanism and does not require the presence of the kidneys.
Richer
C
C
Doussau
M P
MP
Giudicelli
J F
JF
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003655:Decerebrate State; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009392:Nephrectomy; D020913:Perindopril; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D011810:Quinoxalines; D000804:Angiotensin II; D000068438:Brimonidine Tartrate; D000803:Angiotensin I; C014282:cirazoline; D020913:Perindopril