title: Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia.
abstract: Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered NG-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. A does of 40 mg/kg/day increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heart/body weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14C]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14C]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with focal myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular medial proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO.
authors.affiliation: Department of Pathology, University of South Alabama, Mobile 36617, USA.
authors.forename: P
authors.initials: P
authors.lastname: Babál
authors.forename: O
authors.initials: O
authors.lastname: Pechánová
authors.forename: I
authors.initials: I
authors.lastname: Bernátová
authors.forename: S
authors.initials: S
authors.lastname: Stvrtina
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004719:Endomyocardial Fibrosis / Q000201:enzymology / Q000473:pathology*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester