Effect of clonidine and propranolol on venous smooth muscle from spontaneously hypertensive rats.
Clonidine and propranolol reverse arterial smooth muscle hypertrophy in hypertensive animals. It is uncertain whether this is mediated by a reduction in pressure or withdrawal of sympathetic nerve activity to the vasculature. Veins obtained from spontaneously hypertensive rats undergo hypertrophy and thereby provide a model for the separation of pressure-dependent and independent effects of antihypertensive drugs. Clonidine (0.075 and 0.3 mg/kg/day) or propranolol (0.75 and 3.0 mg/kg/day), administered by Alzet minipump for three consecutive weeks to SHR and age and sex matched Wistar-Kyoto normotensive rats (WKY), produced dose-related reductions in systolic arterial pressure, without affecting central or portal venous or right ventricular pressure. Clonidine reversed the decreased extensibility and the biochemical correlates of hypertrophy which characterized the portal (PV) and vena caval veins (IVC) and pulmonary arteries (PA) obtained from SHR. Moreover, clonidine decreased the uptake of PAS-Schiff stain for neutral and acidic glycosaminoglycans (GAG's) and decreased the medial wall thickness of the PV, IVC and PA obtained from SHR. Clonidine did not affect these parameters in blood vessels obtained from WKY. Propranolol exerted actions similar to clonidine, but its effects were more variable and less effective than clonidine, despite equivalent reductions in arterial pressure. The data support the conclusion that clonidine can reverse the functional morphological derangements of venous and PA dysfunction in SHR. The effects appear to be independent of both a reduction in pressure and withdrawal of sympathetic tone to the blood vessels. The data suggest that clonidine, and to a lesser extent propranolol, may act directly on the veins, or indirectly by inhibiting the release or synthesis of a trophic nonadrenergic factor, to reverse the functional and structural changes in the veins.
D000818:Animals; D001834:Body Water / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D050356:Lipid Metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006025:Glycosaminoglycans; D009124:Muscle Proteins; D011506:Proteins; D011433:Propranolol; D003000:Clonidine