Predicted effects of nitric oxide and superoxide on the vasoactivity of the afferent arteriole

Abstract

We expanded a published mathematical model of an afferent arteriole smooth muscle cell in rat kidney (Edwards A, Layton, AT. Am J Physiol Renal Physiol 306: F34–F48, 2014) to understand how nitric oxide (NO) and superoxide (O2−) modulate the arteriolar diameter and its myogenic response. The present model includes the kinetics of NO and O2− formation, diffusion, and reaction. Also included are the effects of NO and its second messenger cGMP on cellular Ca2+ uptake and efflux, Ca2+-activated K+ currents, and myosin light chain phosphatase activity. The model considers as well pressure-induced increases in O2− production, O2−-mediated regulation of L-type Ca2+ channel conductance, and increased O2− production in spontaneous hypertensive rats (SHR). Our results indicate that elevated O2− production in SHR is sufficient to account for observed differences between normotensive and hypertensive rats in the response of the afferent arteriole to NO synthase inhibition, Tempol, and angiotensin II at baseline perfusion pressures. In vitro, whether the myogenic response is stronger in SHR remains uncertain. Our model predicts that if mechanosensitive cation channels are not modulated by O2−, then fractional changes in diameter induced by pressure elevations should be smaller in SHR than in normotensive rats. Our results also suggest that most NO diffuses out of the smooth muscle cell without being consumed, whereas most O2− is scavenged, by NO and superoxide dismutase. Moreover, the predicted effects of superoxide on arteriolar constriction are not predominantly due to its scavenging of NO.