Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudilinduced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NOdependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats., A. Brunová, M. Bencze, M. Behuliak, J. Zicha., and Obsahuje bibliografii
Baroreflex control of heart rate was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats that were subjected to chronic dietary sodium chloride loading (for 4 weeks) either in youth or only in adulthood, i.e. from the age of 4 or 12 weeks. Using phenylephrine administration to pentobarbital-anesthetized male rats we have demonstrated the decreased baroreflex sensitivity (lower slope for reflex bradycardia) in young prehypertensive SS/Jr rats fed a low-salt diet as compared to age-matched SR/Jr animals. High salt intake further suppressed baroreflex sensitivity in young SS/Jr but not in SR/Jr rats. Baroreflex sensitivity decreased with age in SR/Jr rats, whereas it increased in SS/Jr rats fed a low-salt diet. Thus at the age of 16 weeks baroreflex sensitivity was much higher in SS/Jr than in SR/Jr animals. High salt intake lowered baroreflex sensitivity even in adult SS/Jr rats without affecting it in adult SR/Jr rats. Nevertheless, baroreflex sensitivity was significantly lower in young SS/Jr rats with a severe salt hypertension than in adult ones with a moderate blood pressure elevation. It is concluded that the alterations of baroreflex sensitivity in young inbred SS/Jr rats (including the response to high salt intake) are similar to those described earlier for outbred salt-sensitive Dahl rats. We have, however, disclosed contrasting age-dependent changes of baroreflex sensitivity in both inbred substrains of Dahl rats., J. Nedvídek, J. Zicha., and Obsahuje bibliografii
Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endotheliumdependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of 4th week the systolic blood pressure in the control hHTG group was 148±2 mm Hg and in control normotensive Wistar group 117±3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118±1 mm Hg) and spironolactone (124±4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats., J. Török, I. L'upták, J. Matúšková, O. Pecháňová, J. Zicha, J. Kuneš, F. Šimko., and Obsahuje bibliografii
We investigated the effect of pertussis toxin (PTX) on hypotensive response induced by acetylcholine (ACh) and bradykinin (BK) and on noradrenaline (NA)-induced pressor response in spontaneously hypertensive rats (SHR). Fifteen-week-old Wistar rats and age-matched SHR were used. Half of SHR received PTX (10 μg/kg/i.v.) and the experiments were performed 48 h later. After the anesthesia the right carotid artery was cannulated in order to record blood pressure (BP). The hypotensive response to ACh was enhanced in SHR compared to Wistar rats. After pretreatment of SHR with PTX the hypotensive response to ACh was reduced compared to untreated SHR and it was also diminished in comparison to Wistar rats. Similarly, the hypotensive response to BK was also decreased after PTX pretreatment. The pressor response to NA was increased in SHR compared to Wistar rats. NA-induced pressor response was considerably decreased after PTX pretreatment compared to untreated SHR. In conclusion, the enhancement of hypotensive and pressor responses in SHR was abolished after PTX pretreatment. Our results suggested that the activation of PTX-sensitive inhibitory Gi proteins is involved in the regulation of integrated vasoactive responses in SHR and PTX pretreatment could be effectively used for modification of BP regulation in this type of experimental hypertension., S. Čačányiová, F. Kristek, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy