Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor.
In the present study, we investigated the vasodilator properties of A-type, B-type and C-type natriuretic peptides (ANP, BNP and CNP respectively) and the NO (nitric oxide) donor sin-1 (3-morpholino-sydnonimine) in human by-pass grafts. In contrast with previous studies, the same vessel was used to demonstrate a direct link between cGMP production and functional relaxation. Remnants of the IMA (internal mammary artery) and SV (saphenous vein) were obtained from 82 patients undergoing coronary artery by-pass grafting. The responses to cumulative concentrations of ANP, BNP, CNP and sin-1 in vessel rings pre-contracted with a thromboxane A2 agonist (U46619) were measured in an organ bath. Additionally, intracellular cGMP production after single submaximal dose application of these drugs to vessel rings was determined by a RIA. ANP (P=0.001) and sin-1 (P<0.001) caused significant concentration-dependent relaxation of the IMA. In the SV, only sin-1 (P<0.001) induced marked concentration-dependent relaxation. At a single submaximal concentration, significant relaxation as well as intracellular cGMP production were found in response to ANP, BNP and sin-1 in the IMA. In contrast, in the SV, only sin-1 significantly induced cGMP production and relaxation. There was a moderate, but significant, correlation between intracellular cGMP net production and net relaxation in the IMA. In conclusion, ANP, as the most powerful relaxant of all the natriuretic peptides tested on the IMA, may be a possible alternative vasorelaxant to overcome peri-operative vasospasm in this artery. In contrast with sin-1, ANP and BNP were not effective vasorelaxants of the SV. Net relaxation in response to natriuretic peptides correlated with cGMP net concentrations in the IMA.
Hammerer-Lercher
Angelika
A
Division of Clinical Biochemistry, Innsbruck Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria. angelika.lercher@uibk.ac.at
Fersterer
Johann
J
Holzmann
Sigrid
S
Bonatti
Johannes
J
Ruttmann
Elfriede
E
Hoefer
Daniel
D
Mair
Johannes
J
Puschendorf
Bernd
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001026:Coronary Artery Bypass; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D045265:Natriuretic Peptides / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D045265:Natriuretic Peptides; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; C002385:linsidomine; D009320:Atrial Natriuretic Factor; D008981:Molsidomine; D006152:Cyclic GMP