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Long-Term Effect of
Molsidomine and Pentaerythrityl Tetranitrate on Cardiovascular
System of Spontaneously Hypertensive Rats
F. KRISTEK, V. FÁBEROVÁ1, I. VARGA2
Institute of Normal and Pathological Physiology,
Slovak Academy of Sciences, Bratislava, 1Drug Research
Institute, Modra and 2Slovakofarma, Joint Stock Company,
Hlohovec, Slovak Republic
Received July 19, 2002
Accepted November 25, 2002
Summary
We studied the effects of long-term administration of molsidomine and
pentaerythrityl tetranitrate (PETN) on the cardiovascular system of
spontaneously hypertensive rats (SHR). One control and three experimental groups
of
10-week-old animals were used: 1) control Wistar rats, 2) SHR, 3) SHR treated
with molsidomine in tap water (100 mg/kg/day, by gavage), and 4) SHR treated
with PETN in tap water (200 mg/kg/day, by gavage). After six weeks, the content
of cGMP in platelets and NO synthase (NOS) activity in aortas were evaluated in
the experimental groups. For morphological evaluation the rats were perfused at
120 mm Hg with a glutaraldehyde fixative and the arteries were processed for
electron microscopy. Blood pressure and heart weight/body weight ratio (HW/BW)
were increased in all experimental groups with respect to the controls. HW/BW
was lower in the molsidomine group in comparison to both SHR and PETN-treated
group. The platelet content of cGMP was increased and the activity of NOS in the
aortas was decreased in the molsidomine and PETN-treated groups. Wall thickness
and cross-sectional area of thoracic aorta, carotid artery and coronary artery
were increased similarly in all experimental groups compared to the controls,
but there were no differences among the experimental groups. We summarize that
long-term administration of exogenous NO donors did not improve pathological
changes of the cardiovascular system in SHR.
Key words
Spontaneously hypertensive rat • Nitric oxide donors • Cyclic GMP
• Nitric oxide synthase activity • Morphometry
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