Cerebrocortical oxygen supply of sclerotic rats and acute diltiazem therapy

The therapeutic effects of calcium antagonist diltiazem on cerebrovascular smooth muscle of sclerotic and normal rats has been investigated. Arteriosclerosis was caused by treatment of the rats with a water soluble 1,25-dihydro-cholecalciferol in a dose of 97,000 IU. After 2-4 days, serum urea of the treated animals was increased from 56 +/- 8 to 78 +/- 17 mg/dl. Histological examinations of tissue probes from kidneys, heart, aorta and the major arteries by means of the staining method according to von Kossa clearly showed the picture of the Mönckeberg-type atherosclerosis. The calcified rats (N = 23) and the control group (N = 25) were anesthetized with ketamine/xylazine. Following craniotomy and tracheotomy for artificial ventilation, surface PO2 of the cerebro-cortex and cerebral blood flow via the inhalatory hydrogen clearance technique were measured. Surface PO2 frequency distribution of vitamin D3 treated animals showed a left shift (mean +/- SD = 29 +/- 8 compared with 34 +/- 6 mm Hg for controls) and a CBF decrease (1.36 +/- 0.51 compared to 1.50 +/- 0.60 ml/g.min for the controls). Diltiazem infusion of 2 ml/h corresponding to 5 micrograms/kg bw after 5 minutes caused a slight CBF decrease (1.50 +/- 0.60 to 1.43 +/- 0.78 ml/g.min) in controls and an insignificant CBF reduction in sclerotic rats. Mean arterial blood pressure was lowered by diltiazem infusion. The hypertensive sclerotic rats became almost normal (148 +/- 18 to 91 +/- 15 mm Hg) while the control animals decreased in MAP from 118 to 80 +/- 15 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)