Summary
Effects of the calcium-channel antagonist, nitrendipine, on the autoregulation of regional cerebral blood flow were studied by analysing the pressure-flow relationship in the cortex, subcortex and thalamus in pithed anesthetized rabbits. Arterial pressure was altered from 50 to 125 mm Hg by electrical stimulation of the spinal nerve roots. Regional blood flow was measured with the hydrogen clearance technique. Under control conditions, regional blood flow in the cortex, subcortex and thalamus did not change significantly within the range of mean arterial pressures of 50 to 100 mm Hg. Vascular resistance in each region rose significantly (P < 0.05) in a pressure-dependent manner. During the intravenous infusion of nitrendipine (0.3 and 1 μg · kg−1 · min−1), blood flow to the three regions of the brain increased in a pressure-dependent manner when mean arterial pressure was increased from 50 to 125 mm Hg. The autoregulatory increase in regional vascular resistance was abolished. In addition, nitrendipine produced a blood pressure-dependent decrease of the vascular resistance in the subcortex and thalamus but not in the cortex. These results indicate that nitrendipine increases regional cerebral blood flows and suppresses regional autoregulations simultaneously. The autoregulatory adjustment in the cortex is more resistant to nitrendipine than that in the subcortex and thalamus. The observation that the action of nitrendipine was not the same in the three brain regions may be due to the vascular beds of these regions differing in their calciumchannel equipment.
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References
Bolt GR, Saxena PR (1984) Acute systemic and regional hemodynamic effects of felodipine, a new calcium antagonist, in conscious renal hypertensive rabbits. J Cardiovasc Pharmacol 6:707–712
Cauvin C, Loutzenhiser R, Van Breemen C (1983) Mechanisms of calcium antagonist-induced vasodilation. Ann Rev Pharmacol 23:373–396
Fitch W, MacKenzie ET, Harper AM (1975) Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system. Circ Res 37:550–557
Fleckenstein-Grün G, Makita Y, Byon YK, Fleckenstein A (1985) Effect of Ca2+-agonistic and Ca2+-antagonistic 1,4-dihydropyridine compounds on tonic and phasic activation of extramural coronary vasculature. In: Fleckenstein A, Van Breemen C, Gross R, Hoffmcister F (eds) Cardiovascular effects of dihydropyridine-type calcium antagonists and agonists. Springer, Berlin Heidelberg New York Tokyo, pp 290–305
Harper AM (1966) Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiat 29:398–403
Harper AM, Craigen I, Kazda S (1981) Effect of the calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate. J Cereb Blood Flow Metabol 1:349–356
Hasegawa T, Ravens JR, Tool JF, Winston-Salem (1976) Precapillary arteriovenous anastomoses. Arch Neurol 16:217–224
Haws CW, Heistad DD (1984) Effects of nimodipine on cerebral vasoconstrictor responses. Am J Physiol 247:H170-H176
Heistad DD, Kontos HA (1983) Cerebral circulation. In: Shepherd JT, Abboud FM (eds) Handbook of physiology. Section 2: the cardiovascular system, vol 111, part 1. American Physiological Society, Bethesda, pp 137–182
Høedt-Rasmussen K, Sveinsdottir E, Lassen NA (1966) Regional cerebral blood flow in man determined by intra-arterial injection of radioactive inert gas. Circ Res 18:237–247
Hof RP (1983) Calcium antagonist and the peripheral circulation: differences and similarities between PY108-068, nicardipine, verapamil and diltiazem. Br J Pharmacol 78:375–394
Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson Jr JL (1978) Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371-H383
MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK (1976) Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circ Res 39:33–41
MacKenzie ET, Farrar JK, Fitch W, Graham DI, Gregory PC, Harper AM (1979) Effects of hemorrhagic hypotension on the cerebral circulation. I. Cerebral blood flow and pial arteriolar caliber. Stroke 10:711–718
Mayhan WG, Heistad DD (1985) Effect of flordipine on cerebral blood flow. J Pharmacol Exp Ther 235:92–97
Mohamed AA, Mendelow AD, Teasdale GM, Harper AM, McCulloch J (1985) Effect of the calcium antagonist nimodipine on local cerebral blood flow and metabolic coupling. J Cereb Blood Flow Metabol 5:26–33
Pearce WJ, Bevan JA (1987) Diltiazem and autoregulation of canine cerebral blood flow. J Pharmacol Exp Ther 242:812–817
Sawyer CH, Everett JW, Green JD (1954) The rabbit diencephalon in stereotaxic coordinates. J Comp Neurol 110:801–824
Stoepel K, Heise A, Kazda S (1981) Pharmacological studies of the antihypertensive effect of nitrendipine. Arzneim Forsch 31:2056–2061
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Aihara, K. Effects of nitrendipine on the autoregulation of regional cerebral blood flow in the pithed rabbit. Naunyn-Schmiedeberg's Arch. Pharmacol. 339, 469–473 (1989). https://doi.org/10.1007/BF00736063
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DOI: https://doi.org/10.1007/BF00736063