Prazosin administration enhances proliferation of arteriolar adventitial fibroblasts.
Chronic vasodilation stimulates the formation of new arterioles in skeletal muscle, a process that requires the differentiation of mesenchymally derived precursor cells on the abluminal surface of capillaries. Fibroblast proliferation and migration to the arterializing capillary likely precede this differentiation process. In the current study, we investigated the effects of chronic vasodilation with the alpha1 adrenergic blocker prazosin, a treatment that produces enhanced terminal arteriolar development, on the proliferation of fibroblasts present in the adventitia of transverse arterioles. Dual-immunofluorescence labeling for the smooth muscle contractile protein SM-myosin heavy chain (MHC) and for bromodeoxyuridine (BRDU) uptake revealed that prazosin treatment for 4 days stimulated a threefold increase in the density of proliferating fibroblasts surrounding transverse arteriolar trees. This increase was primarily due to an eightfold increase in the density of S-phase fibroblasts surrounding <8 micron m diameter terminal arterioles and a 280% increase in the density of S-phase fibroblasts surrounding 8- to 12-micron m terminal arterioles. Alcian blue counterstaining indicated that no proliferating cells were mast cells. An in vitro study demonstrated that prazosin, at concentrations of 0.5 and 0.05 mg/liter, has no direct effect on fibroblast proliferation. It is concluded that chronic vasodilation with prazosin, a treatment that elicits elevated levels of hemodynamic stress, stimulates the proliferation of adventitial fibroblasts, particularly at the terminal endings of transverse arteriolar trees.
Price
R J
RJ
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
Skalak
T C
TC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply; D018995:Myosin Heavy Chains / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase; D014664:Vasodilation / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004247:DNA; D018995:Myosin Heavy Chains; D001973:Bromodeoxyuridine; D011224:Prazosin