Nitric oxide modulates the interaction of pressure-induced wall mechanics and myogenic response of rat intramural coronary arterioles

Interactions between the biomechanical characteristics and pressure-induced active response of coronary microvessels are still not well known. We tested the hypothesis that pressure-dependent biomechanical characteristics of the coronary vascular wall are modulated by the active myogenic response and local vasodilators. We have utilized data obtained previously in isolated rat intramural coronary arterioles (approximately 100 microm in diameter), in which the diameter was investigated as a function of intraluminal pressure (Szekeres et al.: J. Cardiovasc. Pharmacol., 43, 242-249, 2004). To characterize the magnitude of myogenic response, diameter was expressed as percent of passive diameter as a function of pressure (normalized diameter; ND). In addition, circumferential wall stress (WS) and incremental distensibility (ID) were calculated. In control conditions, after an initial increase between 0-30 mm Hg, ND decreased substantially as pressure increased from 30 to 150 mm Hg. Correspondingly, WS gradually increased as a function of pressure (from 0.3 +/- 0.03 to 34.7 +/- 4.4 kPa) exhibiting a plateau phase between 40-80 mm Hg. In contrast, ID decreased and reached negative values (min: -104.9 +/- 21.9 10(-6) m2/N at 50 mm Hg). Inhibition of nitric oxide (NO) synthase by L-NNA decreased basal diameter (approximately 35% at 2 mm Hg), eliminated pressure-induced changes in ND, reduced the slope of pressure-WS curve, and decreased ID at lower pressures. Simultaneous administration of L-NNA and adenosine (which restored initial diameter, i.e. length of smooth muscle) restored--in part--the pressure-induced reduction in ND, reversed the pressure-induced behavior of WS to control, but not that of ID. These results not only confirm that in coronary arterioles wall stress is regulated by the myogenic response, but also suggest that there is interplay between the mechanical behavior of the wall and the myogenic response. Furthermore, the presence of NO seems to be necessary for maintaining a higher distensibility of intramural coronary arterioles allowing increases in diameter to lower pressures, which then activate the myogenic mechanism resulting in constrictions and full development of myogenic tone, as indicated by the presence of negative slope of pressure-diameter curve in the presence of NO.