The interaction of nitric oxide and prostaglandins in the control of corporal smooth muscle tone: evidence for production of a cyclooxygenase-derivedendothelium-contracting factor

Objective To investigate the interaction of endothelium-derived nitric oxid e (NO) and prostaglandins (PGs) in regulating corporal smooth muscle tone i n vitro. Materials and methods Strips of rabbit corpus cavernosum were mounted in or gan chambers for the measurement of isometric tension. Strips were submaxim ally contracted with noradrenaline and concentration-response curves (CRCs) to acetylcholine (ACh) were constructed before and after treatment with 5 mu mol/L atropine, 20 mu mol of the cyclooxygenase inhibitor indomethacin a nd 10 mu mol of the PGH(2)/thromboxane A(2) receptor antagonist SQ29548. Th e NO synthase (NOS) inhibitors L-N-G-monomethyl arginine (L-NMMA) and L-N-G -nitroarginine (L-NOARG) were added to strips at tonic tension in the prese nce and absence of indomethacin, and after this CRCs to ACh were constructe d. Results The addition of ACh to strips produced a concentration-dependent re laxation which was inhibited by atropine. Indomethacin, but not SQ29548, si gnificantly increased relaxation to ACh. Relaxation to ACh was impaired by L-NMMA, but adding ACh to strips treated with L-NOARG resulted in contracti le responses, whilst both effects were reversed by indomethacin, L-NMMA and L-NOARG led to increases in tonic tone which were unaffected by indomethac in. Conclusions In rabbit corpus cavernosum there is a tonic release of NO whic h does not. appear to be inhibited by a vasoconstrictor prostanoid. Endothe lium-dependent relaxation to ACh results in the dual production of NO and a cyclooxygenase-derived endothelium contracting factor which acts in opposi tion to NO; this factor is unlikely to act on PGH(2)/TXA(2) receptors.