Following Skelton's procedure with unilateral adrenonephrectomy, contralateral adrenal enucleation and application of 1% NaCl with drinking fluid, normal rats develop hypertension and generalized severe arteriosclerosis within 7 weeks, experimental group I. Thereby the mean systolic blood pressure increased from 108 +/- 10 to 223 +/- 12 mm Hg, and 90 arteriosclerotic blood vessels could be counted in 100 histological sections (10 from each animal) of the hearts. Following Skelton's procedure and admixture of flunarizine with the food (40 mg flunarizine per kg for 8 weeks, started 1 week before the operation; mean plasma flunarizine value: 336 +/- 136 ng/ml at the end of the experiment), experimental group II, all rats developed hypertension too, whereby the mean systolic blood pressure increased from 109 +/- 10 to 214 +/- 16 mm Hg, but in contrast to experimental group I, only one artery with sclerosis could be observed in 100 comparable histological sections of the hearts. The untreated control rats, experimental group III, remained normotensive, and no arteriosclerotic blood vessels could be observed. The findings presented show that the calcium-antagonist flunarizine with the dosage used does not reduce hypertension, but almost completely suppresses hypertension-induced arteriosclerosis of the myocardial blood vessels without lowering the high blood pressure.
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Proc Natl Acad Sci U S A
January 2025
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