Inhibition of nitric oxide in rats. Regulation of cardiovascular structure and expression of insulin-like growth factor I and its receptor messenger RNA.
OBJECTIVE
To determine whether 12 days' treatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in spite of the increased arterial load, resulted in a growth-inhibitory response in the heart, aorta and skeletal muscle vascular bed, and whether the presence of L-NAME affected the expression of insulin-like growth factor-I and its receptor messenger RNA (mRNA).


METHODS
Wistar rats were treated orally either with 100 mg/kg L-NAME or with tap water. On days 2, 4, 7 and 12 after initiation of treatment, the systolic blood pressure/mean arterial blood pressure and heart rate were measured, rats were killed and their heart and aorta were excised. Insulin-like growth factor-I and its receptor mRNA were quantitated by solution hybridization assay. On day 12 resistance properties in the skeletal muscle vascular bed were measured by using an in-vivo constant-flow preparation.


RESULTS
The blood pressure in L-NAME-treated rats was increased immediately after initiation of treatment and it continued to increase throughout the experimental period. No hypertrophy was noted in the heart. Moreover, a 21% (P < 0.05) decrease in the right: left ventricular weight ratio indicated that attenuation of growth of the right ventricle had occurred. Increased expression of insulin-like growth factor-I and its receptor mRNA was observed neither in the heart nor in the aorta. The skeletal muscle vascular bed showed a 26% increased resistance at maximal vasodilatation (P < 0.05), which was indicative of a reduced average lumen size. A lower than expected perfusion pressure at maximal vasoconstriction was observed (17% above control, P < 0.05), implicating only modest medial thickening.


CONCLUSIONS
L-NAME hypertension caused a prompt increase in blood pressure, which led neither to left ventricular hypertrophy nor to the expected overexpression of left ventricular/aortic insulin-like growth factor-I mRNA and only to partial structural adaptation in the skeletal muscle vasculature. These findings suggest that augmented expression of insulin-like growth factor-I and its receptor could be mandatory for conveying an appropriate adaptive hypertrophic response, at least in the heart.
Wickman
A
A
Department of Physiology, Göteborg University, Sweden.
Isgaard
J
J
Adams
M A
MA
Friberg
P
P
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000254:growth & development*; D006339:Heart Rate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000235:genetics*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D017526:Receptor, IGF Type 1; D019331:NG-Nitroarginine Methyl Ester