The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats.
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.
Berg
Torill
T
Department of Physiology, Institute for Basic Medical Sciences, University of Oslo, P.O. Box 1103, Blindern, 0317 Oslo, Norway. torill.berg@basalmed.uio.no
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000315:Adrenalectomy; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000077770:Amifampridine; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010646:Phentolamine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D018674:Adrenergic Antagonists; D057911:Angiotensin Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D011719:Pyrazines; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D013449:Sulfonamides; C121226:ZD 1611; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D019311:Staurosporine; D019808:Losartan; D000077770:Amifampridine; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin; D007213:Indomethacin; D010646:Phentolamine