Prostaglandins reduce the contractile responses to noradrenaline and angiotensin II in canine femoral arteries after but not before chronic inhibition of nitric oxide synthesis.
This study was designed to compare the contractile responses to graded concentrations of noradrenaline (1 nM-100 microM) and angiotensin II (0.1-100 nM) of femoral arteries isolated from normal control dogs and from dogs after long-term inhibition of nitric oxide (NO) by N(omega)-nitro-L-arginine (L-NNA; 20 mg/kg/day for 7 days). Maximal contraction to noradrenaline was similar in rings obtained from control and L-NNA-treated dogs. In the latter, however, sensitivity to noradrenaline was reduced compared with control rings, whether the endothelium was present [50% effective concentration (EC50) = 6.04 +/- 0.06 vs. 6.37 +/- 0.08; p < 0.01] or absent (EC50 = 6.00 +/- 0.11 vs. 6.45 +/- 0.05; p < 0.01). Indomethacin reversed this hyporesponsiveness to noradrenaline in arteries obtained from L-NNA-treated dogs but had no effect in rings isolated from control dogs. An almost complete inhibition of the contractile response to angiotensin II, also reversed by indomethacin, was observed in arteries taken from L-NNA-treated dogs both in the presence and in the absence of endothelium. These results suggest that the cyclooxygenase pathway might be upregulated in the smooth muscle cells of canine femoral arteries after long-term inhibition of NO synthesis and that relaxing prostanoids mediate the hypocontractile response of these arteries to both noradrenaline and angiotensin II.
Puybasset
L
L
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, France.
Béverelli
F
F
Giudicelli
J F
JF
Berdeaux
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D000804:Angiotensin II; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine; D007213:Indomethacin