| 12694813 |
Berg T: The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats. Eur J Pharmacol. 2003 Apr 18;466(3):301-10.
The K+ channel inhibitor 4-aminopyridine induced an immediate increase in blood pressure and tension in spontaneously hypertensive rats (SHR). Further analysis strongly suggested this to be due to closure of vascular smooth muscle K+ channels, as previously concluded for normotensive rats (WKY). The tension response was greater in SHR than WKY, suggesting an increased channel activity in order to compensate for the high total peripheral vascular resistance in SHR. The response was enhanced after nitric oxide (NO) synthase inhibitor in both strains, probably reflecting increased channel activity after elimination of the NO-cGMP pathway. The response in SHR but not WKY was increased after alpha (1)-adrenoceptor inhibition and adrenalectomy but not sympathetic nerve transmitter depletion. It increased also after angiotensin AT (1) and endothelin ET (A) receptor antagonists and protein kinase C inhibitor. These results indicated an increased adrenal catecholamine, angiotensin AT (1) and endothelin ET (A) activation of the phospholipase C-protein kinase C pathway in SHR, inhibiting the 4-aminopyridine-sensitive K+ channels. |
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