Basic Research in Cardiology

, Volume 91, Issue 3, pp 248–255 | Cite as

Chronic nitric oxide inhibition as a model of hypertensive heart muscle disease

  • H. MorenoJr.
  • K. Metze
  • A. C. Bento
  • E. Antunes
  • R. Zatz
  • G. de Nucci
Original Contribution


We have compared the myocardial alterations in rats made hypertensive by the chronic inhibition of nitric oxide biosynthesis with those having renal hypertension (two kidney-one clip model). Male Wistar rats were chronically administered the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) for 2, 4 and 8 weeks. Both groups initially developed a similar increase in blood pressure but only the 2K-1C rats developed myocardial hypertrophy after 2–4 weeks. L-NAME-treated animals developed a similar degree of hypertrophy following 8 weeks of treatment. As observed by light microscopy, the myocardial alterations in the latter animals consisted of extensive areas of fibrosis and myocardial necrosis, especially in regions of the subendocardium. The histological alterations induced by L-NAME were not caused by the accompanying hypertension, since the 2K-1C animals had a similar increase in arterial blood pressure without any significant alterations in the heart morphology. 2K-1C rats treated chronically with L-NAME behaved in a manner similar to the L-NAME-treated animals with regard to both the blood pressure increases and cardiac morphological alterations. Animals which received the inactive enantiomer D-NAME did not develop hypertension nor did they have any morphological abnormalities. Both the coronary flow and the contractile capacity of hearts isolated from rats treated with L-NAME for 8 weeks were impaired compared to control animals. These results indicate that the chronic inhibition of NO biosynthesis causes cardiac ischemia associated with a mechanical dysfunction that is unrelated to cardiac hypertrophy which is similar to those seen in some patients suffering from chronic arterial hypertension.

Key words

Endothelium L-NAME arterial hypertension left ventricular hypertrophy myocardial ischemia 


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Copyright information

© Steinkopff Verlag 1996

Authors and Affiliations

  • H. MorenoJr.
    • 1
  • K. Metze
    • 2
  • A. C. Bento
    • 1
  • E. Antunes
    • 1
  • R. Zatz
    • 3
  • G. de Nucci
    • 1
  1. 1.Department of Pharmacology Faculty of Medical SciencesUNICAMPCampinas (SP)Brazil
  2. 2.Department of Pathology Faculty of Medical SciencesUNICAMPCampinas (SP)Brazil
  3. 3.Department of NephrologyUniversity of São Paulo School of MedicineSão PauloBrazil

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