Human urotensin II increases coronary perfusion pressure in the isolated rat heart: potentiation by nitric oxide synthase and cyclooxygenase inhibition.
Urotensin II (U-II) is a cyclic peptide, recently cloned in man and present in cardiac tissue and arteries. The effects of human U-II (hU-II) on coronary perfusion pressure (CPP) were investigated in isolated rat hearts perfused retrogradely via the aorta at constant flow. hU-II produced a concentration-dependent increase in CPP (pEC50 8.6 +/- 0.3, n = 8), the maximum increase in CPP (12 +/- 4 mmHg) was obtained at 10(-7) M hU-II. At higher concentrations of hU-II CPP fell back towards baseline. Endothelin-1 produced a maximum increase in CPP of 63 +/- 11 mmHg within the concentration-range studied. Addition of the NO synthase inhibitor L N(G)nitro-arginine methyl ester (10(-4) M) and the cyclooxygenase inhibitor, indomethacin (10(-5) M) to the perfusion solution had no effect on the pEC50 value for hU-II, but significantly increased the maximum constriction (to 34 +/- 7 mmHg, n = 8, p < 0.05) and inhibited the later dilator response to hU-II. These results suggest that receptors for hU-II are present in the coronary vasculature and that smooth muscle contraction is modulated by the release of dilator factors, including NO and prostacyclin. Endothelial function is therefore likely to be of primary importance in modulating the coronary vasoconstrictor effects of hU-II in vivo.
Gray
G A
GA
Centre for Cardiovascular Science, University of Edinburgh, Dept of Biomedical Sciences, Scotland, UK. gillian.gray@ed.ac.uk
Jones
M R
MR
Sharif
I
I
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000378:metabolism / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
D002317:Cardiovascular Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014579:Urotensins; D014662:Vasoconstrictor Agents; C029677:urotensin II; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin