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

Abstract

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.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

“…(5) resistance of arterial cell populations to oxidative stress, an imperative consequence of inflammation [92][93][94]; and (6) better vasoreactivity [95][96][97][98][99] and anti-thrombotic profile [100,101] of arterial ECs and VSMCs. As ECs play a key role in maintaining physiological vasodilation in response to blood pressure, have angiocrine function in terms of released extracellular vesicles and soluble factors, and ensure resistance of blood vessels to thrombosis [1][2][3][4][5], reciprocal and beneficial interactions between HCAECs and HITAECs might be of pathophysiological significance but largely depend on their heterogeneity.…”

“…The reasons behind the superiority of MAG over SAG might include a higher mechanical competence of anastomoses between the ITA, radial artery, and coronary artery because all of them are muscular arteries with a similar histoarchitecture and diameter [60][61][62][63][64][65][66][67][68][69], relatively low (≈25%) collagen content, optimal glycosaminoglycan profile and negligible protease activity in the arterial wall [70][71][72][73], quiescent profile of arterial vascular smooth muscle cells (VSMCs) [60,[74][75][76][77][78][79][80][81][82][83], higher local secretion of vasodilators (e.g., nitric oxide) by ITA as compared to SV [84][85][86][87][88][89][90][91], resistance to oxidative stress [92][93][94], favourable paracrine interactions between human coronary artery endothelial cells (HCAECs) and human internal thoracic artery endothelial cells (HITAECs) [91], and better vasoreactivity of muscular arteries in response to vasoactive substances [95][96][97][98][99] in conjunction with their anti-thrombotic profile…”

Co-Culture of Primary Human Coronary Artery and Internal Thoracic Artery Endothelial Cells Results in Mutually Beneficial Paracrine Interactions

“…Nonetheless, elevated release of NO by HITAECs and the correspondingly increased vasoreactivity of the ITA [24][25][26] provide for its higher vasodilation in response to the biochemical cues and blood pressure alterations [25,[50][51][52].…”

Differential Effects of Natriuretic Peptides on Arterial and Venous Coronary Artery Bypass Conduits

“…Data on the effects of natriuretic peptides and NPRs on human internal mammary artery and saphenous vein are limited, and our study has assessed the natriuretic peptides effect on the radial artery [18, 19]. To avoid many confounding effects, we studied only patients from whom all three vessels were obtained.…”