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Chronic Disturbances in NO Production Results in Histochemical and Subcellular Alterations of the Rat Heart
N. Tribulová, Ľ. Okruhlicová, I. Bernátová1, O.
Pecháňová1
Institute for Heart Research, Slovak Academy of
Sciences and 1Institute of Normal and Pathological Physiology, Slovak Academy
of Sciences, Bratislava, Slovak Republic
Received July 30, 1999
Accepted September 21, 1999
Summary
The mechanisms and myocardial alterations associated with NO-deficient hypertension are
still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to
examine the influence of captopril treatment. Wistar rats were administered either L-NAME
(40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4
weeks. A significant increase of blood pressure confirmed the reliability of the model.
The results showed that long-lasting L-NAME administration was accompanied by a decrease
of endothelial NO-synthase activity and by a significant local decrease of the following
enzyme activities: capillary-related alkaline phosphatase, 5’-nucleotidase and ATPase
(but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase,
succinic dehydrogenase, ß-hydroxybutyrate dehydrogenase and ATPases. No activity of these
enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and
dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical
changes correlated with subcellular changes, which were characterized by 1) apparent
fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous
population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of
capillaries as well as by induction of angiogenesis. Similar alterations were also found
in the heart of captopril co-treated rats, despite of the significant suppression of blood
pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic
disturbances and ultrastructural alterations of the heart and these changes are probably
not induced by the renin-angiotensin system only.
Key words
Nitric oxide · Hypertension · Histochemistry · Ultrastructure · Captopril
Reprint requests
N. Tribulová, Ph.D., Institute for Heart Research, Slovak Academy of Sciences, Dubravská
cesta 9, 842 33 Bratislava, Slovak Republic. e-mail: usrdtri@savba.sk
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