Enalapril treatment alters the contribution of epoxyeicosatrienoic acids but not gap junctions to endothelium-derived hyperpolarizing factor activity in mesenteric arteries of spontaneously hypertensive rats.
Reduction in endothelium-derived hyperpolarizing factor (EDHF)-mediated dilatory function in large, elastic arteries during hypertension is reversed after blood pressure normalization. We investigated whether similar mechanisms occurred in smaller mesenteric resistance arteries from aged Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs), and SHRs treated with the angiotensin-converting enzyme inhibitor, enalapril, using immunohistochemistry, serial-section electron microscopy, electrophysiology and wire myography. Unlike the superior mesenteric artery, EDHF relaxations in muscular mesenteric arteries were not reduced in SHRs, although morphological differences were found in the endothelium and smooth muscle. In WKY rats, SHRs and enalapril-treated SHRs, relaxations were mediated by small-, large-, and intermediate-conductance calcium-activated potassium channels, which were distributed in the endothelium, smooth muscle, and both layers, respectively. However, only WKY hyperpolarizations and relaxations were sensitive to gap junction blockers, and these arteries expressed more endothelial and myoendothelial gap junctions than arteries from SHRs. Responses in WKY rats, but not SHRs, were also reduced by inhibitors of epoxyeicosatrienoic acids (EETs), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) and miconazole, although sensitivity to EET regioisomers was endothelium-independent in all rats. Enalapril treatment of SHRs reduced blood pressure and restored sensitivity to 14,15-EEZE, but not to gap junction blockers, and failed to reverse the morphological changes. In conclusion, the mechanisms underlying EDHF in muscular mesenteric arteries differ between WKY rats and SHRs, with gap junctions and EETs involved only in WKY rats. However, reduction of blood pressure in SHRs with enalapril restored a role for EETs, but not gap junctions, without reversing morphological changes, suggesting a differential control of chemical and structural alterations.
Ellis
Anthie
A
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra ACT 0200, Australia.
Goto
Kenichi
K
Chaston
Daniel J
DJ
Brackenbury
Therese D
TD
Meaney
Kate R
KR
Falck
J R
JR
Wojcikiewicz
Richard J H
RJ
Hill
Caryl E
CE
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001685:Biological Factors / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001095:Arachidonic Acids; D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D004656:Enalapril