Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2 - production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat., M. M. Govender, A. Nadar., and Obsahuje bibliografii
Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectomized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of DA antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and DA actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of DA through D2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of DA through D1 receptors and in other part by inhibition of stimulatory action of DA through D2 receptors., C. M. Leite, G. J. R. Machado, R. C. M. Dornelles, C. R. Franci., and Obsahuje bibliografii a bibliografické poznámky
Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main pathogenetic factor in intrauterine growth restriction, elevates fetoplacental vascular resistance (and vasoconstrictor reactivity) and thus, presumably, reduces placental blood flow. We thus hypothesized that alcohol may affect the fetus - in addition to other mechanisms - by altering fetoplacental vascular resistance and/or reactivity. Using isolated, double-perfused rat placenta model, we found that maternal alcohol intake in the last third of gestation doubled the vasoconstrictor responses to angiotensin II but did not affect resting vascular resistance. Reactivity to acute hypoxic challenges was unchanged. Chronic maternal alcohol intake in a rat model alters fetoplacental vasculature reactivity; nevertheless, these changes do not appear as serious as other detrimental effects of alcohol on the fetus., V. Jakoubek, V. Hampl., and Obsahuje bibliografii
Prolonged exposure to alveolar hypoxia induces physiological changes in the pulmonary vasculature that result in the development of pulmonary hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is influenced by vasoconstrictor and vasodilator factors secreted from the endothelium, lung parenchyma and in the circulation. During chronic hypoxia, production of vasoconstrictors such as endothelin-1and angiotensin II is enhanced locally in the lung, while synthesis of vasodilators may be reduced. Altered reactivity to these vasoactive agonists is another physiological consequence of chronic exposure to hypoxia. Enhanced contraction in response to endothelin-1 and angiotensin II, as well as depressed vasodilation in response to endothelium-derived vasodilators, has been documented in models of hypoxic pulmonary hypertension. Chronic hypoxia may also have direct effects on pulmonary vascular smooth muscle cells, modulating receptor population, ion channel activity or signal transduction pathways. Following prolonged hypoxic exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current, membrane depolarization, elevation in resting cytosolic calcium and changes in signal transduction pathways. These changes in the electrophysiological parameters of pulmonary vascular smooth muscle cells are likely associated with an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary arterial myocyte function, changes in synthesis of vasoactive factors and altered vasoresponsiveness to these agents may shift the environment in the lung to one of contraction instead of relaxation, resulting in increased pulmonary vascular resistance and elevated pulmonary arterial pressure., L. A. Shimoda, J. S. K. Sham, J. T. Sylvester., and Obsahuje bibliografii
The influence of chronic angiotensin ATi receptor blockade by specific antibody on the development of genetic hypertension was studied in young spontaneously hypertensive rats (SHR). The immunization of 4-week-old SHR with a small part of the angiotensin ATi receptor molecule attenuated the development of hypertension in these animals. After five subcutaneous injections of the antigen both systolic and diastolic blood pressures were significantly lower (p<0.005) in immunized SHR compared to sham- immunized SHR. No effect on blood pressure was seen in immunized Wistar-Kyoto control rats. We conclude that renin-angiotensin system might be partially involved in the development of hypertension in young spontaneously hypertensive rats because it can be attenuated by a specific antibody raised against a part of the angiotensin ATi receptor.
The aim of the study was to assess whether angiotensin converting enzyme (ACE) inhibition with captopril prevents the development of hypertension and myocardial hypertrophy and affects nitric oxide synthase (NOS) activity in rats. Animals were divided into five groups: control, two groups receiving NG-nitro-L-arginine methyl ester (L-NAME) 20 or 40 mg/kg/day, a group receiving captopril 100 mg/kg/day and a group concomitantly treated with 40 mg/kg/day L-NAME plus 100 mg/kg/day captopril. After four weeks, systolic blood pressure (SBP) significantly increased in both L-NAME groups by 30 % and 34 %, respectively. In the captopril group, SBP significantly decreased by 30 % and in the captopril plus L-NAME group SBP was not changed as compared to the controL Although left ventricular weight/body weight (LVW/BW) ratio in both L-NAME groups was significantly elevated by 19 % and 29 %, respectively, no alterations in LVW/BW ratio were found in the captopril group and captopril plus L-NAME group. In both groups receiving L-NAME, NOS activity significantly decreased by 17 % and 69 % in the heart, by 14 % and 26 % in the aorta, by 60 % and 73 % in the brain and by 13 % and 30 % in the kidney, respectively. Captopril did not influence NO synthase activity in any of the studied tissues. We conclude that captopril prevents the development of hypertension and LV hypertrophy without affecting NO formation.
Previous in vitro studies have shown that vascular smooth muscle cells (VSMC) isolated from the aortae of male spontaneously hypertensive rats (SHR) proliferate more rapidly than those obtained from female SHR. Sex-dependent differences of cytosolic free calcium concentration ([Ca2+]j) were therefore studied in VSMC under basal conditions and after the stimulation by different concentrations of angiotensin II (Ang II). No significant difference in basal [Ca2+]i was found in VSMC from male and female SHR. Angiotensin II significantly increased |Ca2+], in VSMC from both genders. This [Ca2+]j rise elicited by 10'7 and 10~9 M Ang II was more pronounced in cells isolated from males than in those from females. This difference may be attributed to greater mobilisation of intracellular calcium stores in male VSMC. It can be concluded that the cytosolic free calcium response to angiotensin II is augmented in VSMC of male SHR, which also grow more rapidly in response to this peptide hormone.
We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by NG -nitro-Larginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent., M. Chaswal ... [et al.]., and Obsahuje seznam literatury
As a novel gasotrans mitter, h ydrogen sulfide (H 2 S) has vasodilating and antihypertensive effects in cardiovascular system. Thus, we hypothesized that H 2 S might have beneficial effects on thoracic endothelial function in two -kidney one -clip (2K1C) rats, a model of renovascular hypertension. Sodium hydrosulfide (NaHS , 56 μmol/kg /day ) was administrated intra - peritoneally from the third day after the 2K1C operation. Along with the development of hypertension, t he systolic blood pressure (SBP) was measured before the operation and each week thereafter. The oxidative stress wa s determined by measurement of malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity and protein expression of oxidative stress -related proteins (AT 1 R, NADPH oxidase subunits). Acetylcholine (ACh) -induced vasorelaxation and angiotensin I I (Ang II) -induced vasocontraction were performed on isolated thoracic aorta. The SBP w as significantly increased from the first week after operation , and was lowered by NaHS. NaHS supplementation ameliorated endothelial dysfunction. The protein expression of oxidative stress -related proteins were downregulated, while SOD activity upregulated. In conclusion, improvement of endothelial function is involved in the antihypertensive mechanism of H 2 S. The protective effect of H 2 S is attributable to suppression o f vascular oxidative stress that involves inhibition of Ang II -AT 1 R action, downregulation of oxidases, as well as upregulation of antioxidant enzyme., H. Xue, S. Zhou, L. Xiao, Q. Guo, S. Liu, Y. Wu., 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