ALPHA-1-ADRENOCEPTOR BLOCKADE REDUCES THE ANGIOTENSIN-II-INDUCED VASCULAR SMOOTH-MUSCLE CELL-DNA SYNTHESIS IN THE RAT THORACIC AORTA AND CAROTID-ARTERY

We explored effects of alpha-1-adrenoreceptor blockade with prazosin on the increased vascular smooth muscle cell (SMC) DNA synthesis induced by angiotensin II (Ang II) in rats. Ang II was infused with or without prazosin or its solvent. Observations were compared with those in rats receiving saline or solvent. In group A, Ang II was infused for 2 weeks by subcutaneously implanted osmotic minipumps at a rate of 35 ng/100 g per minute. Group B received Ang II together with the alpha-1-adrenoreceptor antagonist prazosin (0.35-mu-g/100 g per minute). Group C received Ang II and 50% dimethyl sulfoxide (DMSO), the solvent of prazosin; group D received 50% DMSO; and group E received 0.9% NaCl (Ang II vehicle). All animals were infused with 5-bromo-2'-deoxyuridine for 2 weeks via separate minipumps to measure DNA synthesis. Ang II significantly increased the fraction of DNA synthesizing SMCs in the media of the thoracic aorta from 0.4 +/- 0.1% (mean +/- SD) in group E (n = 6) to 10.8 +/- 7.0% in group A (n = 8). Addition of prazosin to Ang II reduced the labeling fraction of SMCs to 3.0 +/- 2.2% (group B, n = 9). The remaining SMC DNA synthesis in the prazosin-treated group was probably due to the effects of the solvent of prazosin, i.e., 50% DMSO, since infusion of 50% DMSO alone increased the labeling fraction to 4.1 +/- 2.0% (group D, n = 6). Comparable results were obtained in the carotid artery. Both systolic blood pressures and medial cross-sectional areas increased during Ang II infusion, but these parameters were not altered by prazosin or DMSO. We conclude that alpha-1-adrenoreceptors are, either indirectly or by parallel stimulation, involved in the Ang II-induced increase of medial SMC DNA synthesis in the rat. Stimulation of alpha-1-adrenoreceptors rather than an elevated blood pressure stimulated vascular SMC DNA synthesis.