The resistance of some rat cerebral arteries to the vasorelaxant effect of cromakalim and other K+ channel openers.
1. Cromakalim (0.01-30 microM) and sodium nitroprusside (SNP, 0.01-100 microM) were tested for their ability to relax a number of pre-contracted small arteries (approximate diameter 200-700 microM at 100 mmHg) from the rat, rabbit and guinea-pig. 2. In the rat, SNP (0.01-100 microM) caused near maximal relaxation in all vessels studied including the middle cerebral, anterior cerebellar, basilar, mesenteric and renal arteries. Cromakalim (0.01-30 microM) relaxed pre-contracted mesenteric and renal arteries but was only a weak relaxant of all the rat cerebral arteries with the exception of the basilar artery. Similar experiments using mesenteric and cerebral vessels from the rabbit and guinea-pig showed cromakalim could relax pre-contracted vessels in a concentration-dependent manner. 3. Two other K+ channel openers, nicorandil and pinacidil, were also tested for their ability to relax rat cerebral arteries. Nicorandil (0.01-100 microM) was ineffective in the rat anterior cerebellar artery at concentrations up to 100 microM. Pinacidil (0.01-100 microM) caused significant vasorelaxation, although high concentrations were required (greater than 10 microM) and the response was insensitive to the effects of glibenclamide (3 microM). 4. Electrophysiological experiments with the rat anterior cerebellar artery showed that cromakalim (up to 30 microM) failed to influence the resting membrane potential of impaled single smooth muscle cells. 5. The results showed that some rat small cerebral arteries were resistant to the effects of K+ channel openers including cromakalim, pinacidil and nicorandil. This is peculiar to this vascular tree since the same vessels from other species do not exhibit the same behaviour. Such a phenomenon could result from a lack of K+ channels opened by cromakalim in rat cerebral arteries.
McPherson
G A
GA
Baker Medical Research Institute, Prahran, Victoria, Australia.
Stork
A P
AP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002531:Cerebellum / Q000098:blood supply; D002536:Cerebral Arteries / Q000187:drug effects*; D019806:Cromakalim; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D009569:Nitric Oxide / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D009569:Nitric Oxide; D020110:Pinacidil; D005996:Nitroglycerin; D000109:Acetylcholine