Endothelin-1 modulates cyclic GMP production and relaxation in human pulmonary vessels.
The aim of this study was to examine the effects of endothelin-1 (ET-1) on sodium nitroprusside (SNP) induced relaxation and cyclic 3',5'-guanosine monophosphate (cGMP) accumulation in human pulmonary vessels. The basal levels of cGMP were similar in arteries (2.48 +/- 0.24 pmol/mg protein; n = 7) and veins (3.25 +/- 0.24 pmol/mg protein; n = 7). In tissues (n = 7) treated with N omega-nitro-L-arginine and indomethacin, cGMP values were significantly reduced (arteries, 1.30 +/- 0.24 pmol/mg protein and veins, 1.95 +/- 0.28 pmol/mg protein). In treated tissues, SNP (10 microM) increased the cGMP level by 10-fold in arteries and veins. ET-1 (0.02 and 0.2 microM) reduced significantly the cGMP increase in SNP-stimulated vessels. This inhibition was greater in veins (76%) when compared with arteries (34%). Norepinephrine (10 microM) did not affect the cGMP levels. The sensitivity and the maximal relaxation induced by SNP in veins contracted with ET-1 (0.2 microM) was significantly diminished (in comparison with norepinephrine; 10 microM). In arteries, SNP relaxations were not altered by ET-1 contraction. Inasmuch as 8-bromo-cyclic 3',5' guanosine monophosphate curves were not altered by ET-1 treatment in either arteries or veins, the relaxant mechanisms that are downstream of guanylate cyclase activation apparently are not affected. These results suggest that ET-1 may play a role in the control of muscle tone in the human pulmonary vascular bed by modifying cGMP levels associated with vasorelaxant agonist stimulation.
Pussard
G
G
CNRS URA 1159, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Gascard
J P
JP
Gorenne
I
I
Labat
C
C
Norel
X
X
Dulmet
E
E
Brink
C
C
D006152:Cyclic GMP / Q000096:biosynthesis*; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D009599:Nitroprusside; D006152:Cyclic GMP; D009638:Norepinephrine