Greater vasodepressor sensitivity to nicardipine in spontaneously hypertensive rats (SHR) compared to normotensive rats.
Differences in the degree of attenuation by the calcium entry blocker, nicardipine, of the pressor responses to alpha-1 (phenylephrine) and alpha-2 (UK 14.304) adrenoceptor agonists was investigated in pentobarbital-anesthetized, normotensive Sprague-Dawley (SD) or Wistar Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR), treated with the ganglionic blocking agent, pentolinium. Following administration of the ganglionic blocking agent, pentolinium, nicardipine produced a significant fall in blood pressure in SHR but not in SD or WKY rats. Nicardipine had no effect on the basal blood pressure of pithed SHR. In rats treated with the ganglionic blocking agent, pentolinium, nicardipine produced parallel shifts to the right in the dose-response curves for phenylephrine but had no effect on maximal responses to phenylephrine. The decrease in the ED50 of phenylephrine was greater in the SHR than in normotensive rats. Nicardipine produced a decrease in both the ED50 and the maximal response to the alpha-2 adrenoceptor agonist, UK 14.304. The decrease in the maximal response was greater in SHR than in WKY normotensive rats but the change in ED50 for UK 14.304 was greater in WKY than in SHR. SD normotensive rats gave intermediate results. We conclude that the inhibition of alpha-adrenoceptor-mediated pressor responses by nicardipine is generally more pronounced in SHR than in normotensive rats. This suggests that hypertension may be accompanied by an increase in the sensitivity of peripheral resistance beds to calcium entry blockers.
Atkinson
J
J
Laboratoire de Pharmacologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Nancy I, France.
Sautel
M
M
Sonnay
M
M
Fluckiger
J P
JP
de Rivaz
J C
JC
Boillat
N
N
Piton
M C
MC
Porchet
P A
PA
Armstrong
J M
JM
Fouda
A K
AK
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003655:Decerebrate State; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D010425:Pentolinium Tartrate; D009529:Nicardipine