The interaction of nitric oxide and prostaglandins in the control of corporal smooth muscle tone: evidence for production of a cyclooxygenase-derived endothelium-contracting factor.
OBJECTIVE
To investigate the interaction of endothelium-derived nitric oxide (NO) and prostaglandins (PGs) in regulating corporal smooth muscle tone in vitro. Materials and methods Strips of rabbit corpus cavernosum were mounted in organ chambers for the measurement of isometric tension. Strips were submaximally contracted with noradrenaline and concentration-response curves (CRCs) to acetylcholine (ACh) were constructed before and after treatment with 5 micromol/L atropine, 20 micromol of the cyclooxygenase inhibitor indomethacin and 10 micromol of the PGH2/thromboxane A2 receptor antagonist SQ29548. The NO synthase (NOS) inhibitors L-NG-monomethyl arginine (L-NMMA) and L-NG-nitroarginine (L-NOARG) were added to strips at tonic tension in the presence and absence of indomethacin, and after this CRCs to ACh were constructed.


RESULTS
The addition of ACh to strips produced a concentration-dependent relaxation which was inhibited by atropine. Indomethacin, but not SQ29548, significantly increased relaxation to ACh. Relaxation to ACh was impaired by L-NMMA, but adding ACh to strips treated with L-NOARG resulted in contractile responses, whilst both effects were reversed by indomethacin. L-NMMA and L-NOARG led to increases in tonic tone which were unaffected by indomethacin.


CONCLUSIONS
In rabbit corpus cavernosum there is a tonic release of NO which does not appear to be inhibited by a vasoconstrictor prostanoid. Endothelium-dependent relaxation to ACh results in the dual production of NO and a cyclooxygenase-derived endothelium contracting factor which acts in opposition to NO; this factor is unlikely to act on PGH2/TXA2 receptors.
Minhas
S
S
Department of Urology, St James University Hospital, Leeds, UK.
Cartledge
J J
JJ
Eardley
I
I
Joyce
A D
AD
Morrison
J F
JF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C045749:SQ 29548; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin