Diltiazem selectively inhibits cerebrovascular extrinsic but not intrinsic myogenic tone. A review.
The tone of blood vessels resulting from extrinsic influences is dependent on activator calcium derived from sequestered cellular and also extracellular sources. Experiments on rabbit blood vessels in vitro show that--in comparison to systemic vessels--the contractions of cerebral arteries are proportionately more dependent on extracellular calcium and have sequestered calcium sources that are more easily depleted. Both these observations suggest that activator calcium mechanisms differ at least quantitatively in cerebral compared to noncerebral vessels. Diltiazem antagonizes agonist-induced tone in cerebral arteries at a lower concentration than is required in systemic arteries and veins. For example, the concentration of diltiazem to halve the response of the rabbit basilar artery to norepinephrine (ED50) is 1 X 10(-8) M, whereas those for the ear and mesenteric arteries and the saphenous vein are 10.4, 2.0, and 1.8 X 10(-7) M, respectively. A similar selectivity has been found to K+ and serotonin-induced contractions. It has been argued that the neuroeffector mechanism in the portal vein reflects that in systemic resistance vessels. The drug is effective against the spontaneous rhythmic activity of the longitudinal muscle of the vein, reducing it to half at 1.5 X 10(-7) M. Diltiazem is relatively ineffective in antagonizing intrinsic smooth muscle tone, both cerebral (basilar) and extracerebral (facial vein) requiring ED50 values of 4 and 5 X 10(-4) M, respectively. In summary, our in vitro experiments on rabbit tissue show that diltiazem selectively antagonizes cerebrovascular extrinsic but not intrinsic tone.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply*; D004110:Diltiazem / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D001552:Benzazepines; D007473:Ion Channels; D004110:Diltiazem; D009638:Norepinephrine