Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels.
The present study was designed to elucidate whether the conduction of vasomotor responses mediated by endothelium-derived hyperpolarizing factor (EDHF) in rat mesenteric arteries is altered during hypertension. Iontophoresed acetylcholine (ACh; 500 ms) caused EDHF-mediated hyperpolarization and vasodilatation at the local site and these responses spread through the endothelium to remote sites in 12-week-old Wistar-Kyoto rats (WKY). Conducted responses were significantly attenuated in age-matched spontaneously hypertensive rats (SHR) although the rate of decay with distance did not change. Inhibition of inwardly rectifying potassium (Kir) channels (30 microM barium) eliminated the difference between WKY and SHR by attenuating conducted responses in WKY but not SHR. At the local site, barium (30 microM) significantly reduced the duration but not the amplitude of ACh-induced hyperpolarization in WKY only. Barium had no effect when the iontophoretic stimulus was reduced to 350 ms. After blockade of EDHF in SHR, ACh elicited a depolarization which our indirect data suggest spreads along the vessel in the endothelium. Messenger RNA expression of Kir2.0 genes did not differ between the strains nor did the amplitude of K(+)-induced hyperpolarization, which was abolished by disruption of the endothelium. Immunohistochemistry revealed a decrease in connexin (Cx)37 but not Cx40 or Cx43 protein in endothelial cells of SHR compared to WKY. Results suggest that conduction of EDHF-mediated responses in WKY, but not in SHR, is facilitated by activation of Kir channels at the site of ACh application and not by differences in endothelial connexin expression. Lack of Kir channel involvement in hypertension may result from reduction in the duration of the hyperpolarization due to the development of ACh-mediated depolarization, rather than to any difference in Kir subunit expression or function.
Goto
Kenichi
K
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 0200, Australia. kenichi.goto@anu.edu.au
Rummery
Nicole M
NM
Grayson
T Hilton
TH
Hill
Caryl E
CE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001835:Body Weight; D017630:Connexins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D017630:Connexins; C489461:Kir2.1 channel; C489463:Kir2.2 channel; C489465:Kir2.4 channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D014665:Vasodilator Agents; D001464:Barium; D000109:Acetylcholine; D011188:Potassium