Expression of Constitutive and Inducible Nitric Oxide Synthases in the Vascular Wall of Young and Aging Rats

• Published in: Circulation research Vol. 83; no. 3; pp. 279 - 286
• Main Authors: Cernadas, Maria R, Sanchez de Miguel, Lourdes, Garcia-Duran, Margarita, Gonzalez-Fernandez, Fernando, Millas, Inmaculada, Monton, Mercedes, Rodrigo, Jose, Rico, Luis, Fernandez, Patricia, de Frutos, Trinidad, Rodriguez-Feo, Juan A, Guerra, Jose, Caramelo, Carlos, Casado, Santos, Lopez-Farre, Antonio
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 10.08.1998; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Acetylcholine - pharmacology; Aging - metabolism; Animals; Aorta - metabolism; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Blood vessels and receptors; Bradykinin - pharmacology; Calcium - metabolism; Cattle; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Enzyme Induction; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Male; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroprusside - pharmacology; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system; Immunohistochemistry; Rat; Enzyme; Isozyme; Ageing; Rodentia; 3',5'-GMP; Gene expression; Artery; Young animal; Nitric-oxide synthase; Vertebrata; Mammalia; Enzymatic activity; Blood vessel; Nitric oxide; Aged animal; Aorta; Circulatory system; Oxidoreductases; Endothelium derived relaxing factor; Calcium Cations
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.83.3.279

Two NO synthase (NOS) isoforms have been described in vessels, an endothelial constitutive NOS (eNOS) and an inducible NOS (iNOS). The purpose of the present study was to examine the endothelium-dependent and endothelium-independent hypotensive response in aging rats, analyzing the ability of their vessels to produce NO. The studies were performed in 2 groups of euvolemic, conscious, male Wistar ratsaging rats (n=20, 18 months old) and young rats (n=20, 5 months old). The hypotensive responses to acetylcholine, bradykinin, and sodium nitroprusside were determined. Furthermore, the expression of the NOS isoforms by Western blot and the eNOS and iNOS activities, defined as Ca and Ca conversion of [() C]L-arginine into [() C]L-citrulline, respectively, were also determined. In the aging rats, we found an impaired hypotensive response to acetylcholine and bradykinin (2 NO-and endothelium-dependent hypotensive agents) that was accompanied by a preserved hypotensive response to sodium nitroprusside. Aging rats also demonstrated an enhanced sensitivity response to the pressor effect of the L-arginine antagonist L-N and a reduced vasoconstrictor response to angiotensin II. The inhibition of NO synthesis normalized the pressor effect of angiotensin II in the aging animals. Nitrite plus nitrate plasma levels were increased in aging rats. Furthermore, cGMP content was also higher in the aging vessels. In the aging aortas, the expression of both eNOS and iNOS isoforms was enhanced. However, in aging rats, the activity of the eNOS isoform was markedly reduced, a finding that was accompanied by the presence of iNOS activity. The vessel wall of aging rats showed an enhanced expression of eNOS and iNOS isoforms. However, eNOS activity was reduced in the aging animals. These findings could explain the impaired endothelium-dependent hypotensive response associated with aging. (Circ Res. 1998;83:279-286.)