Alpha 1-adrenoreceptor 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 micrograms/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).(ABSTRACT TRUNCATED AT 250 WORDS)
van Kleef
E M
EM
Department of Pathology, University of Limburg, Maastricht, The Netherlands.
Smits
J F
JF
De Mey
J G
JG
Cleutjens
J P
JP
Lombardi
D M
DM
Schwartz
S M
SM
Daemen
M J
MJ
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure; D002339:Carotid Arteries; D004247:DNA / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D004247:DNA; D011224:Prazosin; D004121:Dimethyl Sulfoxide