Mechanical compression elicits NO-dependent increases in coronary flow

Abstract

Our previous studies have demonstrated that a decrease in arteriolar diameter that causes endothelial deformation elicits the release of nitric oxide (NO). Thus we hypothesized that cardiac contraction, via deformation of coronary vessels, elicits the release of NO and increases in coronary flow. Coronary flow was measured at a constant perfusion pressure of 80 mmHg in Langendorff preparations of rat hearts. Hearts were placed in a sealed chamber surrounded with perfusion solution. The chamber pressure could be increased from 0 to 80 mmHg to generate extracardiac compression. To minimize the impact of metabolic vasodilatation and rhythmic changes in shear stress, nonbeating hearts, by perfusing the hearts with a solution containing 20 mM KCl, were used. After extracardiac compression for 10 or 20 s, coronary flow increased significantly, concurrent with an increased release of nitrite into the coronary effluent and increased phosphorylation of endothelial NO synthase in the hearts. Inhibition of NO synthesis eliminated the compression-induced increases in coronary flow. Shear stressinduced dilation could not account for this increased coronary flow. Furthermore, in isolated coronary arterioles, without intraluminal flow, the release of vascular compression elicited a NO-dependent dilation. Thus this study reveals a new mechanism that, via coronary vascular deformation, elicited by cardiac contraction, stimulates the endothelium to release NO, leading to increased coronary perfusion. endothelial deformation; nitric oxide; coronary circulation WE DEMONSTRATED PREVIOUSLY that a brief compression of single isolated mesenteric arterioles elicits an endothelium-dependent, nitric oxide (NO)-mediated dilation. Also, a unidirectional compression of cultured endothelial cells stimulates, time dependently, the release of NO from the cells (26). These studies indicate that vascular deformation coincident with endothelial deformation induced by physical forces stimulates endothelial cells to produce vasoactive substances to regulate vascular tone.Multiple mechanisms are involved in the regulation of the coronary circulation, among them cardiac metabolism (8), as well as local mechanisms including myogenic constriction (12,18,20) and flow-induced dilation (13, 23), all of which have been demonstrated to participate significantly in the control of vascular resistance. It is well known that in the coronary circulation, vessels are rhythmically compressed by contraction of the myocardium. Unlike the physical forces exerted by pulsatile pressure, in which the vessels are subjected to circumferential stretch (1), myocardial contraction provides for circumferential compression of the vessels. Thus studies aimed to evaluate the physiological significance of cardiac contraction in the regulation of the coronary circulation become of considerable interest, because they may implicate this physical force as being a factor in the local regulation of myocardial blood flow.Given that endothelial deformation caused by changes in vascular di...

Mechanical compression elicits vasodilatation in rat skeletal muscle feed arteries

“…An increase in guanylate cyclase activity, indicating an increase in NO release, was demonstrated in the effluent from rhythmically compressed femoral artery rings (LaMontagne et al 1992). In coronary arterioles, dilatation in response to longer periods of constant extravascular pressure (20-60 s) was NO dependent (Sun et al 2004). To our knowledge, there have been no previous studies examining vascular deformation and the release of prostaglandins or endothelium-derived hyperpolarizing factor.…”

Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles

“…The mechanism by which the increase in smooth muscle [Ca 2ϩ ] i leads to increase in endothelial [Ca 2ϩ ] i is not addressed in the present study. Myoendothelial coupling in afferent arterioles may allow diffusion of Ca 2ϩ or IP 3 through gap junction (3,14,25,26), and release of extracellular messengers may occur or opening of mechanosensitive endothelial cation channels may be initiated by the vasoconstriction (8,20,(22)(23)(24)32). The latter mechanism may provide one explanation of why calcium is transferred from smooth muscle to endothelium during vasoconstriction, while an increase in endothelial [Ca 2ϩ ] i induced by acetylcholine was not transferred to the smooth muscle cells.…”

“…Based on these findings, they suggested that a vasoconstrictor-mediated increase in smooth muscle [Ca 2ϩ ] i is transferred to the endothelial cells where it activates endothelial NO synthase and enhances formation of NO, which diffuses back to the smooth muscle and reduces/buffers contraction. On the other hand, deformation of the endothelium during vasoconstriction and consequent release of NO have also been described (22,23).…”

Role of retrograde flow in the shear stimulus associated with exercise blood flow

“…(2006) has demonstrated that pulse pressure eliciting mechanical deformation of isolated rat soleus feed arteries can significantly increase vasodilation, which was partly mediated by the vascular endothelium. Thus, it is uncertain in the present study whether the fast contraction velocity stimulated a greater release of vasoactive substances than the slow contraction velocity through the mechanical strain of the vessel wall associated with muscle contractions (Sun et al. , 2004) or by the haemodynamic shear stress produced by rhythmic exercise.…”