Vasodilator actions of flunarizine in isolated dog cerebral and extracerebral arteries.

Abstract

Abstract-Flunarizine relaxed isolated canine arteries precontracted with pro staglandin (PG) F2a, epithio-methano-thromboxane A2 and K+; the relaxation was in the order of cerebral >renal>mesenteric= coronary arteries, when contracted with PGF2a or the thromboxane A2 analogue. Flunarizine-induced relaxation was unaffected by treatment with atropine, propranolol, cimetidine, chlorpheniramine, aminophylline and indomethacin, and by removal of endothelium.Under normoxia, flunarizine attenuated contractions elicited by Ca2+ in the K+-stimulated cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media to a greater extent than that in PGF2a-stimulated preparations.The Ca2+-induced contraction in cerebral arteries was more sensitive to flunarizine than that in mesen teric arteries.Contractions caused by PGF2a in Ca2+-free media were not influenced by flunarizine.

Vasodilator Effects of Flunarizine on Retinal Blood Vessels in Anesthetized Rats

“…7,8) Several similarities between retinal and cerebral vasculature have been recognized. 9,10) For example, 1) retinal endothelial cells form the blood-retinal barrier with a similar function as the blood-brain barrier, 26,27) and 2) an autoregulatory mechanism for blood flow is present in the retinal and optic nerve head circulation as in the cerebral circulation.…”

“…7,8) Because the retinal vasculature anatomically and functionally resembles the cerebral vasculature, 9,10) flunarizine may produce a potent vasodilator effect on retinal blood vessels. Indeed, flunarizine was shown to improve the blood flow to the optic nerve head in patients with lowtension glaucoma.…”

SELECTIVE EFFECTS OF LOMERIZINE, A NOVEL DIPHENYLMETHYLPIPERAZINE Ca2+ CHANNEL BLOCKER, ON CEREBRAL BLOOD FLOW IN RATS AND DOGS

“…data, 1992). 10,24 In actual fact, the Ca 2ϩ channel blockers in general have relatively selective effects on cerebral arteries over peripheral arteries, [25][26][27][28] possibly because cerebral arteries are more dependent on extracellular Ca 2ϩ for their activation than are peripheral arteries. 23 Finally, intravenous injections of lomerizine have been shown to increase VBF more than blood flow in peripheral arteries (such as the mesenteric and femoral arteries) in dogs.…”

Effects of prostaglandin F2 alpha and thromboxane A2 analogue on bovine cerebral arterial tone and calcium fluxes.

“…17 ' 18 Prostanoid-induced constriction of isolated cerebral arteries is calcium-dependent but is partially resistant to inhibition by CAts such as nifedipine, 5 nimodipine, 58 ' 19 nicardipine, 20 -21 diltiazem, 22 or flunarizine. 23 The mechanism of resistance to CAts is not known. If CAts inhibit prostanoid-induced Ca 2+ uptake through CAt-sensitive channels in cerebrovascular smooth muscle, 24 then CAt-resistant constriction could be due to Ca 2+ uptake through CAt-insensitive channels, Ca 2+ release from intracellular stores such as the sarcoplasmic reticulum, or other mechanisms.…”

“…The data obtained were expressed as desaturation curves (which demonstrate the decline of strip 45 Ca content with time) and as curves showing the fractional rate of 45 Ca efflux (percentage of 45 Ca lost per minute). 23 In all experiments, arterial rings or strips were selected at random to receive a drug or special treatment. Data are expressed as mean+SEM, with n^6 rings or strips from at least five different animals for each variable.…”