Long-term effect of molsidomine and pentaerythrityl tetranitrate on cardiovascular system of spontaneously hypertensive rats.
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.
Kristek
F
F
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic. Kristek@unpf.savba.sk
Fáberová
V
V
Varga
I
I
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010417:Pentaerythritol Tetranitrate / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP