Altered EDHF‐mediated dilation in spontaneously hypertensive rats following enalapril treatment

Abstract

Endothelium derived hyperpolarising factor (EDHF) plays a prominent role in resistance arteries via a variety of different mechanisms. We examined these mechanisms in first order mesenteric arterial branches from Wistar‐Kyoto (WKY), spontaneously hypertensive rats (SHR) and age‐matched SHR with blood pressure normalized by enalapril (30 mg/kg/day, 8 wks), using serial section electron microscopy and wire myography in the presence of L‐NAME (100 microM) and indomethacin (10 microM). EDHF‐mediated dilations to acetylcholine (ACh) were sensitive in all three groups to the combination of BKCa, IKCa and SKCa channel inhibitors, iberiotoxin (100 nM), apamin (500 nM) and TRAM‐34 (500 nM). However, only responses in WKY were sensitive to the combined gap junction antagonists, 37,43gap 27, 40gap 40 and 43gap 26 (100 microM each), while responses in both WKY and enalapril treated SHR were sensitive to the selective inhibitor of epoxyeicosatrienoic acid derivatives (EETs), 14,15‐EEZE (10 microM). Electron microscopy showed significantly fewer myoendothelial gap junctions (MEGJs) in SHR than in WKY and no change following enalapril treatment. In conclusion, responses in WKY are dependent on EETs, MEGJs and BKCa, while responses in SHR are dependent on BKCa but independent of EETs or gap junctions. Reduction in angiotensinII with enalapril restores the involvement of EETs but not gap junctions.