Endothelial control of myogenic tone in mesenteric arteries is impaired after intermittent hypoxia exposure

Abstract

Sleep apnea (SA) is an independent risk factor for hypertension and rats exposed to intermittent hypoxia (IH) develop hypertension. Both animal and clinical studies of SA report elevated vascular contractility and decreased vasodilation but effects on myogenic tone (MT) are not well‐described. Ca2+ sparks hyperpolarize vascular smooth muscle (VSM) to inhibit MT. We reported previously that IH reduces Ca2+ spark frequency and enhances MT in small mesenteric arteries (SMA). In Sham but not IH SMA, endothelium removal enhanced MT and reduced Ca2+ spark frequency. We hypothesized that endothelial‐derived NO stimulates VSM Ca2+ sparks to inhibit MT in Sham but not IH SMA. We found that NOS inhibition (L‐NNA, 100 μM) had no effect on MT in either IH or Sham SMA (27±5 vs. 23±10 in E‐IH, 10±2 vs 10±2% in Sham). We also observed no effect of cyclooxygenase inhibition (aspirin, 10 μM) or cytochrome P450 inhibition (SKF 525A, 10 μM). However, vessel distensibility was greater in IH than in Sham SMA (0.7±0.1 vs. 0.5±0.1 p<0.05). Denuding enhanced distensibility in Sham but not IH arteries so that distensibility, like MT and spark frequency was not different between IH and Sham in denuded SMA. These results indicate that the endothelial factor(s) that augments Ca2+ spark frequency and inhibits pressure‐induced MT is lost after IH exposure and is not NO, a COX product or a CYP product. This factor may also restrict arterial distensibility.