D-003 DIFFERENT EFFECT OF LONG-TERM NEURONAL NO-SYNTHASE INHIBITION ON CARDIOVASCULAR SYSTEM OF SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR RATS

Abstract

Background The study demonstrates the long-term effect of neuronal NO-synthase (nNOS) inhibitor 7-nitroindazole (7-NI) on blood pressure (BP), heart, coronary artery and thoracic aorta of spontaneously hypertensive rats (SHR) and Wistar rats. Methods Ten weeks old animals were divided in four groups (20 rats in each): Wistar rats, SHR, and Wistar rats and SHR administered 7-NI (10 mg/kg b.w./day) for 6 weeks in tap water. BP was measured by the plethysmographic method weekly. For morphological study ten animals of each group were perfused with a glutaraldehyde fixative (120 mm Hg). Coronary artery and thoracic aortawere processed for electron microscopy. Tunica intima and media of the arteries were investigated. In ten rats thoracic aorta was cut into rings and used for functional study. Results 7-NI administered to Wistar rats (compared to Wistar rats) did not affect BP but heart/body weight was decreased. Hypotrophy of both vessels was observed (decrease of wall thickness - WT, cross sectional area - CSA, and WT/inner diameter – WT/ID). In coronary artery CSA of endothelial and smooth muscle cells markedly decreased while CSA of extracellular matrix did not change. Noradrenaline-induced contraction of the aorta was attenuated. 7-NI in SHR (compared to SHR) did not affect BP but heart/body weight was increased. Morphological investigation of coronary artery revealed hypertrophy of the wall (increased WT, CSA, and WT/ID) and increased CSA of endothelial cells, smooth muscle cells, and extracellular matrix. In the aorta no changes in trophicity as well as in noradrenaline-induced contraction was found. Conclusion Long-term administration of 7-NI to normotensive Wistar rats evoked pressure independent cardiac hypotrophy and arterial wall hypotrophy due to decrease of endothelial and smooth muscle cell mass, which was associated with decreased contractile efficiency. 7-NI administered to SHR had no effect on the structure and vasoactive properties of the aorta but it evoked hypertrophy of the heart and coronary artery wall. We suggest that different effect of 7-NI in Wistar rats and SHR could be evoked by affecting the different regulatory pathways or by affecting the same pathways which might have different activity in normotension and hypertension. Supported by VEGA grant 2/0111/11, 2/0019/11, SAS-NCP JRP 2010/01.