We evaluated the effects of N G -nitro-L-arginine methylester (L-NAME) (50 mg/kg/day) and 7-nitroindazole (7NI) (10 mg/kg/day) administered from 10th-16th week of age either individually or together on cardiovascular system of Wistar rats and SHR. Systolic blood pressure (sBP) was measured weekly by the plethysmographic method. For morphological studies, the animals (n=10) were perfused with a fixative (120 mm Hg), and thoracic aorta and carotid and co ronary arteries were processed for electron microscopy. For functional investigation (n=10), aortic rings were used in an or gan bath. In Wistar rats, L-NAME evoked an increase of sBP; hype rtrophy of the heart and arterial walls; an increase in cross-sectional areas (CSA) of endothelial cells (EC), muscle cells (SMC), extracellular matrix (ECM), and a decrease in acetylcholin e-induced endothelial-dependent relaxation (EDR). 7NI evoked sBP-independent hypotrophy of the heart and arterial walls, a decrease in CSA of EC and SMC without affecting the CSA of ECM, and a mild decrease in acetylcholine-induced EDR. 7NI and L-NAME administered together evoked lower effect on BP and trophicity of the heart and all arteries, and a similar de crease in acetylcholine-induced EDR compared to L-NAME alone. In SHR, 7NI did not evoke any effect on the studied parameters., F. Kristek, M. Drobna, S. Cacanyiova., and Obsahuje bibliografii
Structural changes of thoracic aorta (TA), carotid (CA) and iliac artery (IA) were assessed in Wistar and spontaneously hypertensive rats (SHR) aged 3, 17, and 52 weeks. Systolic blood pressure (sBP) was measured by plethysmography weekly. After perfusion fixation the arteries were processed for electron microscopy. The wall thickness (WT), cross-sectional area (CSA), inner diameter (ID), and WT/ID in all arteries and volume densities of endothelial cells (ECs), muscle cells (SMCs), and extracellular matrix (ECM) in TA were measured and their CSAs were calculated. In 3-week-old SHR compared to Wistar rats, sBP did not differ; in the TA, all parameters (WT, CSA, ID, WT/ID, CSA of SMCs, CSA of ECs, and CSA of ECM) were decreased; in CA, WT and CSA did not differ, ID was decreased, and WT/ID was increased; in IA, WT, CSA, and ID were increased. In 17- and 52-week-old SHRs, sBP and all parameters in all arteries were increased, only ID in IE in 52-week-old SHRs and CSA of ECs in the TA in 17-week-old SHRs did not change. Disproportionality between BP increase and structural alterations during ontogeny in SHR could reflect the flexibility of the arterial tree to the different needs of supplied areas.
Two exogenous NO donors were used to act as substitutes for impaired endogenous nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks' lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) induced stabilized hypertension. Simultaneously administered isosorbide-5-mononitrate did not prevent the development of hypertension. Molsidomine, administered concomitantly with L-NAME, significantly attenuated the BP increase. However, BP was still found to be moderately increased compared to the initial values. Remarkable alterations in the geometry of the aorta, carotid and coronary artery found in NO-deficient hypertension were prevented in rats administered L-NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the maximum hypotensive value did not differ from the values recorded in the controls or in animals treated with L-NAME plus molsidomine. Notably enough, the hypotension was similar to that found in rats administered L-NAME alone for six weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute and molsidomine substitute only partially the impaired endogenous NO production., M. Gerová, F. Kristek., and Obsahuje bibliografii
Treatment with pertussis toxin (PTX) which eliminates the activity of Gi proteins effectively reduces blood pressure (BP) and vascular resistance in spontaneously hypertensive rats (SHR). In this study we have compared the functional characteristics of isolated arteries from SHR with and without PTX-treatment (10 μg/kg i.v., 48 h before the experiment). Rings of thoracic aorta, superior mesenteric artery and main pulmonary artery were studied under isometric conditions to measure the reactivity of these vessels to receptor agonists and to transmural electrical stimuli. We have found that the treatment of SHR with PTX had no effect on endothelium-dependent relaxation of thoracic aorta induced by acetylcholine. In PTX-treated SHR, the maximum contraction of mesenteric artery to exogenous noradrenaline was reduced and the dose-response curve to cumulative concentration of noradrenaline was shifted to the right. Similarly, a reduction in the magnitude of neurogenic contractions elicited by electrical stimulation of perivascular nerves was observed in the mesenteric artery from PTX-treated SHR. PTX treatment of SHR also abolished the potentiating effect of angiotensin II on neurogenic contractions of the main pulmonary artery. These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension., A. Zemančíková, J. Török, J. Zicha, J. Kuneš., and Obsahuje bibliografii a bibliografické odkazy