Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C097

Oral Communications

A novel role for cyclooxygenase, NO-synthase and soluble guanylyl cyclase in resistance arteries from patients with cardiovascular disease.

M. Matthies1, M. Bloksgaard1, L. P. Riber3, A. Irmukhamedov3, J. G. De Mey1,2,3

1. Department for Cardiovascular and Renal Research, University of Southern Denmark, Odense C, Denmark. 2. Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands. 3. Department of Cardiac, Vascular and Thoracic Surgery, Odense University Hospital, Odense C, Denmark.

We previously reported large relaxing responses (>75%) to the endothelium-dependent vasodilators acetylcholine and bradykinin in pericardial resistance arteries isolated from patients requiring coronary artery bypass or cardiac valve replacement surgery [1-2]. In the present study we determined, in arterial segments in parallel from the same patient in a multi wire-myograph setup, the involvement of prostaglandins and of the NO/cGMP pathway. The use of human materials was approved by the Medical Ethical Committee of the Region of Southern Denmark (S-2010044 and S-20140202) and were performed according to the principles expressed in the Declaration of Helsinki. Informed written consent was obtained from all patients prior to surgery. Relaxing effects of 1 µM Na-nitroprusside (NO-donor) were not reduced by 100 µM L-NAME (NOS-inhibitor) but abolished by 300 µM cPTIO (NO-scavenger) or 10 µM ODQ (inhibitor of guanylyl cyclase). In vessels contracted with 32 mM K+, the relaxing effect of 1 µM bradykinin was, on average, only moderately reduced by L-NAME or ODQ and not by cPTIO. In vessels contracted with 32 mM K+ in the presence of 10 µM indomethacin (non-selective COX-inhibitor), bradykinin-induced relaxation was markedly reduced by L-NAME or ODQ but not significantly modified by cPTIO. In vessels contracted with 0.25-0.5 nM endothelin-1, the strong relaxing effect of bradykinin was not reduced by either L-NAME, cPTIO or ODQ in absence and presence of indomethacin. These findings are in line with earlier observations of a prostaglandin- and NO/cGMP-independent vasodilator pathway in resistance arteries from patients with residual cardiovascular disease. They also indicate for the first time, presence of an additional pathway that is i) sensitive to inhibition of NO-synthase or guanylyl cyclase but not scavenging of NO, ii) modulated by endogenous prostaglandins and iii) unlikely to cause hyperpolarization.

Where applicable, experiments conform with Society ethical requirements