To study the nature of adrenergic stimulation of ions and water reabsorption in the newt renal distal tubule, stationary microperfusion of the nephron and electron probe analysis were used. After application of norepinephrine (NE 10'6 M) to the tubule surface, the fractional reabsorption of fluid increased from 15.0±3.1 to 41.30±10.4 % (n = 7, p<0.01), of Na+ from 69.30 ±6.6 to 79.10±7.5 % (p<0.05), CT from 63.30±7.6 to 72.40 ±7.9 % (p<0.05). Instead of secretion (control), there was reabsorption of K+. Fractional reabsorption of Ca2+ decreased from 51.00±6.0 to 43.00±7.0 % (p<0.05). The nonspecific alpha-adrenergic antagonist dibenamine 10"6 M completely inhibited the effect of NE while, under the action of propranolol (2xl(76 M) NE increased ion and water reabsorption significantly. When applied alone, or with NE, the specific alpha2-adrenoblocker idazoxan, 2xl0‘6 M, did not interfere with reabsorption in the distal tubule. At the same time, under the action of alphai-adrenoblocker prazosin 2xl0'6 M NE, increased the fractional reabsorption of fluid from 24.10 ±3.4 to 44.40 ±4.0 % (n = 6, p<0.001). These results serve as evidence that there exist specific alpha^adrenoceptors in the newt distal tubule the stimulation of which increases membrane permeability of the distal tubule to water, Na+, K+, Cl', but not to Ca2+.
Stress serves as a risk factor in the etiology of hypertension. The present study was designed to decipher the effect and mechanism of chronic stress on the progression of pressure overload-induced cardiac dysfunction. We used abdominal aortic constriction (AAC) to induce pressure overload with or without chronic restraint stress to establish the animal models. Echocardiographic analysis showed pressure overload-induced cardiac dysfunction was worsened by chronic stress. Compared with the AAC rats, there is a significant increase in cardiac hypertrophy, injury, apoptosis and fibrosis of the AAC + stress rats. Furthermore, we found the secretion of norepinephrine (NE) increased after the AAC operation, while the level of NE was higher in the AAC + stress group. Cardiomyocytes and cardiac fibroblasts isolated from neonatal rats were cultured and separately treated with 1, 10, 100 μM NE. The higher concentration NE induced more cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression. These results revealed that high level of NE-induced cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression further contributes to the effect of chronic stress on acceleration of pressure overloadinduced cardiac dysfunction., W. Liu, X. Wang, Z. Mei, J. Gong, X. Gao, Y. Zhao, J. Ma, F. Xie, L. Qian., and Obsahuje bibliografii
This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases., J. Švíglerová, J. Kuncová, L. Nalos, J. Slavíková, M. Štengl., and Obsahuje bibliografii a bibliografické odkazy
Maintenance of norepinephrine (NE)-induced contraction is dependent on Ca2+ influx through L-type voltage-dependent Ca2+ channels (VDCC), which is opposed by nitric oxide. Adrenergic receptors are coupled with different G proteins, including inhibitory G proteins (Gi) that can be inactivated by pertussis toxin (PTX). Our study was aimed to investigate the effects of endothelium removal, PTX pretreatment and acute VDCC blockade by nifedipine on the contractions of femoral arteries stimulated by norepinephrine. We used 12-week-old male WKY, half of the rats being injected with PTX (10 μg/kg i.v., 48 h before the experiment), which considerably reduced their blood pressure (BP). Contractions of isolated arteries were measured using Mulvany-Halpern myograph. NE dose-response curves determined in femoral arteries from PTX-treated WKY rats were shifted to the right compared to those from control WKY. On the contrary, removal of endothelium augmented NE dose-response curves shifting them to the left. Acute VDCC blockade by nifedipine (10-7 M) abolished all differences in NE dose-response curves which were dependent on the presence of either intact endothelium or functional Gi proteins because all NE dose-response curves were identical to the curve seen in vessels with intact endothelium from PTX-treated animals. We can conclude that BP reduction after PTX injection is accompanied by the attenuation of NE-induced contraction of femoral arteries irrespective of endothelium presence. Moreover, our data indicate that both vasodilator action of endothelium and Gi-dependent vasoconstrictor effect of norepinephrine operate via the control of Ca2+ influx through VDCC., S. Líšková, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronized activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions., L. Molcan, A. Vesela, M. Zeman., and Obsahuje bibliografii
A higher mean arterial pressure (MAP) achieved by norepinephrine up-titration may improve organ blood flow in critically ill, whereas norepinephrine-induced afterload rise might worsen myocardial function. Our aim was to assess the effects of norepinephrine dose titration on global hemodynamics in cardiogenic shock. We prospectively evaluated 12 mechanically ventilated euvolemic patients (aged 67±12 years) in cardiogenic shock (10 patients acute myocardial infarction, 1 patient dilated cardiomyopathy, 1 patient decompensated aortic stenosis). Hemodynamic monitoring included arterial and Swan-Ganz catheters. The first data were obtained at MAP of 65 mm Hg, then the norepinephrine dose was increased over 40 min to achieve MAP of 85 mm Hg. Finally, the norepinephrine-dose was tapered over 40 min to achieve MAP of 65 mm Hg. Norepinephrine up-titration increased MAP to the predefined values in all patients with concomitant mild increase in filling pressures and heart rate. Systemic vascular resistance increased, whereas cardiac output remained unchanged. During norepinephrine down-titration, all hemodynamic parameters returned to baseline values. We observed no changes in lactate levels and mixed venous oxygen saturation. Our data suggest that short-term norepinephrine dose up-titration in cardiogenic shock patients treated or pretreated with inotropes was tolerated well by the diseased heart., R. Rokyta, Jr ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Disordered motility is one of the most important pathogenic characteristics of functional dyspepsia (FD), although the underlying mechanisms remain unclear. Since the sympathetic system is important to the regulation of gastrointestinal motility, the present study aimed to investigate the role of norepinephrine (NE) and adrenoceptors in disordered gastric motility in a rat model with FD. The effect of exogenous NE on gastric motility in control and FD rats was measured through an organ bath study. The expression and distribution of β-adrenoceptors were examined by real-time PCR, Western blotting and immunofluorescence. The results showed that endogenous gastric NE was elevated in FD rats, and hyperreactivity of gastric smooth muscle to NE and delayed gastric emptying were observed in the rat model of FD. The mRNA levels of β1-adrenoceptor and norepinephrine transporter (NET) and the protein levels of β2-adrenoceptor and NET were increased significantly in the gastric corpus of FD rats. All three subtypes of β-adrenoceptors were abundantly distributed in the gastric corpus of rats. In conclusion, the enhanced NE and β-adrenoceptors and NETs may be contributed to the disordered gastric motility in FD rats.