Clofibrate retardation of naturally-occurring arteriosclerosis in repeatedly-bred male and female rats.
Repeatedly-bred, male and female Sprague-Dawley rats which develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously were killed at sequential time intervals, i.e., when the females had completed 1, 2, 3 and 4 pregnancies. The control breeders received no treatment; the experimental animals were given 113 mg of clofibrate/100 g of b.w., subcutaneously, daily, 5 times per week. Clofibrate-treated breeders manifested reduction in blood pressure and in the incidence and severity of arterial disease characteristic of repeatedly-bred rats. The aortic lesions of the clofibrate-treated breeders showed attenuation of the usual severe ground substance alterations, the degenerative changes in connective tissue elements, e.g., fibrosis and elastosis, and absence of calcification and cartilaginous metaplasia. Clofibrate-treated breeders did not show any unusual elevation in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, or significant reduction of their hyperlipidemia. They manifested a definite reduction in adrenocortical and medullary histopathology and their circulating corticosterone levels were subnormal compared to non-treated breeders. It is suggested that the protective effect of clofibrate was mediated through its ability to block normal adrenal steroidogenic pathways rather than through its antilipemic action.
D000302:Adrenal Cortex / Q000473:pathology; D000305:Adrenal Cortex Hormones / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002994:Clofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D050356:Lipid Metabolism; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000305:Adrenal Cortex Hormones; D002994:Clofibrate