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Renal Vasoconstriction (renal + vasoconstriction)
Selected AbstractsLack of renal improvement with nonselective endothelin antagonism with tezosentan in type 2 hepatorenal syndrome,,HEPATOLOGY, Issue 1 2008Florence Wong Renal vasoconstriction is a key factor in the development of hepatorenal syndrome (HRS) and may be secondary to increased activities of endothelin-1, a potent renal vasoconstrictor. To assess the effects of tezosentan, a nonselective endothelin receptor antagonist, on renal function in patients with type 2 HRS, six male patients, 56.3 ± 2.5 years old, with cirrhosis and type 2 HRS were treated with tezosentan; ascending doses of 0.3, 1.0, and 3.0 mg/hour, each for 24 hours, were used for the initial 2 patients, but a constant dose of 0.3 mg/hour for up to 7 days was used for the remaining 4 patients. The glomerular filtration rate, renal plasma flow, 24-hour urinary volume, mean arterial pressure (MAP), heart rate, tezosentan levels, and vasoactive hormones were measured daily. Albumin was given as required. The study was stopped early because of concerns about the safety of tezosentan in type 2 HRS. Five patients discontinued the study early; one stopped within 4 hours because of systemic hypotension (MAP < 70 mm Hg), and 4 patients stopped at ,4 days because of concerns about worsening renal function (serum creatinine increased from 180 ± 21 to 222 ± 58 ,mol/L, P > 0.05) and decreasing urine volume (P = 0.03) but without a significant change in MAP. The plasma tezosentan concentrations were 79 ± 34 ng/mL at a steady state during infusion at 0.3 mg/hour. The plasma endothelin-1 concentrations increased from 2.7 ± 0.3 pg/mL at the baseline to 19.1 ± 7.3 pg/mL (P < 0.05). Conclusion: An endothelin receptor blockade potentially can cause a deterioration in renal function in patients with cirrhosis and type 2 HRS. Caution should be taken in future studies using endothelin receptor antagonists in these patients. (HEPATOLOGY 2007.) [source] Calcium handling in afferent arteriolesACTA PHYSIOLOGICA, Issue 4 2004M. Salomonsson Abstract The cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G-protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L-type channels, T-type channels and P/Q channels. A role for non-voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl, channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium-activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl, channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels. [source] Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome,HEPATOLOGY, Issue 6 2007Aleksander Krag Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either terlipressin (N group, n = 11) or a placebo (P group, n = 4), and 8 had refractory ascites and received terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (CNa), lithium clearance (CLi), osmolal clearance (COsm), and urine sodium concentration (UNa) were assessed before and after the injection of 2 mg of terlipressin or the placebo. GFR increased in the N group (69 ± 19 versus 92 ± 25 mL/min, P < 0.005) and in the R group (31 ± 19 versus 41 ± 31 mL/min, P < 0.05) after terlipressin. In the N group, terlipressin induced an increase in CNa (0.89 ± 0.21 versus 1.52 ± 1.45 mL/min, P < 0.05), CLi (17.3 ± 8.9 versus 21.5 ± 11.6 mL/min, P < 0.05), and COsm (2.10 ± 0.81 versus 3.06 ± 2.0 mL/min, P < 0.05). In the R group, terlipressin induced an increase in CNa (0.11 ± 0.18 versus 0.35 ± 0.40 mL/min, P < 0.05) and CLi (5.5 ± 4.2 versus 9.5 ± 8.55 mL/min, P < 0.05). UNa increased in both groups after terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after terlipressin. All parameters remained unchanged after the placebo. Conclusion: The vasopressin 1 receptor agonist terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS. Vasoconstrictors may represent a novel future treatment modality for these patients. (HEPATOLOGY 2007.) [source] Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009G. BRAGADOTTIR Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine-dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post-cardiac surgery patients. Methods: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51chromium,ethylenediaminetetraacetic acid, respectively. RVO2 and RO2Ex were calculated by arterial and renal vein blood samples. Results: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO2, RO2Ex and renal vascular resistance increased dose-dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects. Conclusions: Short-term infusion of low to moderate, non-hypertensive doses of vasopressin induced a post-glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post-cardiac surgery patients. This was accompanied by an increase in RVO2, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship. [source] Changes in renal artery resistance after meal-induced splanchnic vasodilatation in cirrhotic patientsJOURNAL OF CLINICAL ULTRASOUND, Issue 9 2001Pascal Perney MD Abstract Purpose A relationship between vasomotor tone changes in mesenteric and renal vessels in cirrhotic patients has been suspected but remains controversial. The aim of this study was to assess by duplex Doppler sonography the changes in the circulatory resistance of the renal arteries and superior mesenteric artery (SMA) following meal-induced splanchnic vasodilatation. Methods Twenty-seven cirrhotic patients and 15 healthy volunteers with no hepatic or renal dysfunction were prospectively included in the study. The resistance index (RI) of the SMA and of the right and left renal arteries was measured by duplex Doppler sonography before and 30 minutes after ingestion of a standard 400-kcal balanced liquid meal. Values in controls and patients and values before and after the meal were compared, and correlations between RIs, Child-Pugh class (liver function), and creatinine clearance were assessed in cirrhotic patients. Results The fasting renal artery RI was greater in cirrhotic patients than in controls (p < 0.0001), but there was no difference in fasting SMA RIs. After the meal, there was a significant decrease in the SMA RI in controls (0.85 ± 0.04 before versus 0.74 ± 0.03 after meal, p = 0.0001) and in cirrhotic patients (0.85 ± 0.04 before versus 0.77 ± 0.04 after, p = 0.0001) and a significant increase in the renal artery RI (0.57 ± 0.06 before versus 0.62 ± 0.05 after in controls, p = 0.001; 0.68 ± 0.07 before versus 0.70 ± 0.07 after in cirrhotic patients, p = 0.001). No correlation was found in cirrhotic patients between the changes in renal artery RI and the postprandial SMA RI decrease, the Child-Pugh class, or the creatinine clearance. Conclusions Meal-induced SMA vasodilatation (RI decrease) is associated with a marked increase in the renal artery RI, worsening the renal vasoconstriction in cirrhotic patients. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:506,512, 2001. [source] Regional haemodynamic effects of cyclosporine A, tacrolimus and sirolimus in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2004S M Gardiner The observation that the immunosuppressants, cyclosporine A (CsA) and tacrolimus, have pressor effects, but sirolimus does not, has led to an hypothesis that generalised sympathoexcitation, resulting from inhibition of calcineurin by CsA and tacrolimus underlies their pressor effects, because sirolimus does not inhibit calcineurin. It is unknown if sirolimus has haemodynamic actions not accompanied by a pressor effect, and whether or not the pressor effects of CsA and tacrolimus are accompanied by similar haemodynamic changes. Therefore, the first aim of our studies was to investigate these possibilities in conscious, chronically-instrumented, male, Sprague-Dawley rats. CsA (5.9 mg kg,1 bolus i.v.) caused rapid-onset, prolonged hypertension, tachycardia and mesenteric vasoconstriction. There was a slower onset renal vasoconstriction, but no significant change in hindquarters vascular conductance; all the effects of CsA were significantly greater than those of vehicle. CsA given by infusion (over 30 min or 2 h) caused changes qualitatively similar to those above. Repeated administration of CsA over 4 days did not enhance its cardiovascular effects. Pretreatment with the angiotensin (AT1) receptor antagonist, losartan, and the endothelin (ETA and ETB) receptor antagonist, SB 209670, reduced the pressor and mesenteric vasoconstrictor effects of CsA. Additional administration of the , -adrenoceptor antagonist, phentolamine, completely inhibited the cardiovascular effects of CsA. Tacrolimus (450 ,g kg,1 bolus i.v.) caused similar peak pressor and tachycardic effects to CsA, but these were much slower in onset, and were maximal when there were no significant regional vasoconstrictions, indicating that the pressor effect was probably due to a rise in cardiac output. However, although propranolol reversed the tachycardic effect of tacrolimus, it did not influence the pressor response. Sirolimus (450 ,g kg,1 bolus i.v.) had no tachycardic action, and only a modest, transient pressor effect, accompanied by equally brief reductions in renal, mesenteric, and hindquarters vascular conductances. The differences between the regional haemodynamic profiles of equipressor doses of CsA and tacrolimus, and the finding that sirolimus has significant cardiovascular actions, indicate that generalised sympathoexcitation, resulting from calcineurin inhibition (with CsA and tacrolimus), is unlikely to be the sole explanation of their pressor effects. British Journal of Pharmacology (2004) 141, 634,643. doi:10.1038/sj.bjp.0705659 [source] Lipoxygenase and cyclo-oxygenase products in the control of regional kidney blood flow in rabbitsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Jeremy J Oliver Summary 1.,The aim of the present study was to examine the roles of cyclo-oxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonate signalling cascades in the control of regional kidney blood flow. 2.,In pentobarbitone-anaesthetized rabbits treated with NG -nitro- l -arginine and glyceryl trinitrate to ,clamp' nitric oxide, we determined the effects of ibuprofen (a COX inhibitor) and esculetin (a LOX inhibitor) on resting systemic and renal haemodynamics and responses to renal arterial infusions of vasoconstrictors. 3.,Ibuprofen increased mean arterial pressure (14 ± 5%) and reduced medullary laser Doppler flux (MLDF; 26 ± 6%) when administered with esculetin. A similar pattern of responses was observed when ibuprofen was given alone, although the reduction in MLDF was not statistically significant. Esculetin tended to increase renal blood flow (RBF; 16 ± 7%) and MLDF (28 ± 13%) when given alone, but not when combined with ibuprofen. 4.,After vehicle, renal arterial infusions of noradrenaline, angiotensin II and endothelin-1 reduced RBF and cortical laser Doppler flux (CLDF), but not MLDF. In contrast, renal arterial [Phe2,Ile3,Orn8]-vasopressin reduced MLDF but not RBF or CLDF. Ibuprofen alone did not significantly affect these responses. Esculetin, when given alone, but not when combined with ibuprofen, enhanced noradrenaline-induced renal vasoconstriction. In contrast, esculetin did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin, angiotensin II or endothelin-1. 5.,We conclude that COX products contribute to the maintenance of arterial pressure and renal medullary perfusion under ,nitric oxide clamp' conditions, but not to renal haemodynamic responses to the vasoconstrictors we tested. Lipoxygenase products may blunt noradrenaline-induced vasoconstriction, but our observations may, instead, reflect LOX-independent effects of esculetin. [source] Influence of sympathetic and AT1 -receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive ratsACTA PHYSIOLOGICA, Issue 3 2009M. H. Abdulla Abstract Aim:, This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR). Methods:, Forty-eight SHR were subjected to 7 days of losartan (10 mg kg,1 day,1 p.o.), carvedilol (5 mg kg,1 day,1 p.o.) or losartan + carvedilol (10 mg kg,1 day,1 + 5 mg kg,1 day,1 p.o.). On day 8, the rats were anaesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation. Results:, There were significant (P < 0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared with that in untreated rats (all P < 0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared with those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P < 0.05). Conclusion:, Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves, but, following the removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal ,1 -adrenoceptors and AT1 receptors to the vasoactive agents. Co-treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR. [source] | ||||||||||