Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats

Kohtaro Numaguchi, Kensuke Egashira, Masao Takemoto, Toshiaki Kadokami, Hiroaki Shimokawa, Katsuo Sueishi, Akira Takeshita

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    200 Citations (Scopus)

    Abstract

    The aim of the present study was to investigate the effects of long-term blockade of nitric oxide synthesis with the L-arginine analogue Nω-nitro-L-arginine methyl ester (L-NAME) for 8 weeks on coronary vascular and myocardial structural changes. Four groups of Wistar-Kyoto rats were studied: those with no treatment, those treated with L-NAME 1 g/L (3.7 mmol/L in drinking water), those treated with L-NAME 0.1 g/L (0.37 mmol/L in drinking water), and those treated with L-NAME 1.0 g/L and hydralazine 120 mg/L (0.6 mmol/L in drinking water). After 8 weeks, the heart was excised, and the degrees of structural changes in coronary arteries (wall-to-lumen ratio and perivascular fibrosis), myocardial fibrosis, and myocyte size were quantified by an image analyzer. Chronic inhibition of nitric oxide synthesis increased arterial pressure compared with control animals. Chronic inhibition of nitric oxide synthesis caused significant microvascular remodeling (increased wall-to-lumen ratio and perivascular fibrosis). Cardiac hypertrophy was also observed after chronic inhibition of nitric oxide synthesis. Coadministration of hydralazine prevented arterial hypertension but did not affect microvascular remodeling and cardiac hypertrophy induced by the chronic inhibition of nitric oxide synthesis. In addition, chronic inhibition of nitric oxide synthesis caused scattered lesions of myocardial fibrosis, which was significantly attenuated by cotreatment with hydralazine. These results suggest that long-term blockade of nitric oxide synthesis caused coronary microvascular remodeling and cardiac hypertrophy in rats in vivo by a mechanism other than arterial hypertension. In contrast, arterial hypertension contributed to the development of myocardial fibrosis induced by long-term blockade of nitric oxide synthesis.

    Original languageEnglish
    Pages (from-to)957-962
    Number of pages6
    JournalHypertension
    Volume26
    Issue number6 I
    DOIs
    Publication statusPublished - Dec 1995

    All Science Journal Classification (ASJC) codes

    • Internal Medicine

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