Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats

• Published in: Brain research Vol. 1098; no. 1; pp. 196 - 203
• Main Authors: Barer, G.R., Fairlie, J., Slade, J.Y., Ahmed, S., Laude, E.A., Emery, C.J., Thwaites-Bee, D., Oakley, A.E., Barer, D.H., Kalaria, R.N.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 07-07-2006; Amsterdam Elsevier; New York, NY
• Subjects: Angiogenesis; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biomarkers; Blood and lymphatic vessels; Blood vessels; Cardiology. Vascular system; Cardiovascular System - drug effects; Cardiovascular System - enzymology; Cerebrovascular Circulation - physiology; Enzyme Inhibitors - pharmacology; Experimental diseases; Fundamental and applied biological sciences. Psychology; Glucose transporter; Glucose Transporter Type 1 - metabolism; Hypertension; Hypertrophy, Right Ventricular - metabolism; Hypoxia; Hypoxia, Brain - metabolism; Immunohistochemistry; Lung - drug effects; Lung - enzymology; Male; Medical sciences; Microcirculation - drug effects; Microcirculation - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sleep apnea; Sleep. Vigilance; Vertebrates: nervous system and sense organs; Glucose transporter; Hypertension; Angiogenesis; Blood vessels; Hypoxia; Nitric oxide synthase; Sleep apnea; Rat; Central nervous system; Cardiovascular disease; Environmental factor; Glucose; Encephalon; Microcirculation; Apnea; Blood vessel; Inhibition; Carrier protein; Oxygen; Enzyme; Rodentia; Nitric-oxide synthase; Vertebrata; Mammalia; Sleep; Animal; Circulatory system; Oxidoreductases
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.04.098

We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O
2 for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O
2 for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor
N
6-nitro-
l-arginine methyl ester (
l-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with
l-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated.