pituitrin and tezosentan

In recent times, there have been many developments in therapies for acute heart failure, in contrast to the preceding 20 years. These have been mainly fueled by new and expanding knowledge about the pathophysiology of heart failure, which has allowed for insight into potential therapeutic strategies. This review will examine the key emerging therapies for acute heart failure, in light of available pathophysiological and clinical evidence.

Topics: Antidiuretic Hormone Receptor Antagonists; Heart Failure; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Pyridines; Simendan; Tetrazoles; Treatment Outcome; Vasodilator Agents; Vasopressins

During high epidural anaesthesia, endothelin only contributes minimally to blood pressure stabilization. This phenomenon could result from the inhibitory action of nitric oxide on the endothelin system. To clarify this, we studied the interaction between nitric oxide and endothelin during high epidural anaesthesia in conscious dogs, in comparison to the interaction of nitric oxide and vasopressin.. Six animals were used in 45 individual experiments randomly arranged as follows: N-omega-nitro-arginine-methylester 0.3-10 mg kg-1 under physiological conditions or during high epidural anaesthesia (lidocaine 1%) and N-omega-nitro-arginine-methylester (l-NAME) 0.3-10 mg kg-1 after preceding endothelin (Tezosentan(R)) or vasopressin (beta-mercapto-beta,beta-cyclo-penta-methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor blockade under physiological conditions or during high epidural anaesthesia. During control experiments normal saline was injected either intravenously (n = 5) or into the epidural space (n = 4).. N-omega-nitro-arginine-methylester increased mean arterial pressure dose-dependently in all groups. However, this effect was substantially reduced in the presence of the endothelin receptor antagonist compared to N-omega-nitro-arginine-methylester alone, both under control conditions (7 +/- 3 vs. 21 +/- 3 mmHg; P < 0.05) and during high epidural anaesthesia (17 +/- 3 vs. 30 +/- 1 mmHg; P < 0.05). Blockade of vasopressin showed no similar relationship with N-omega-nitro-arginine-methylester.. The diminished increase in mean arterial pressure after injection of N-omega-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.

Topics: Anesthesia, Epidural; Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Dogs; Endothelin Receptor Antagonists; Endothelins; Enzyme Inhibitors; Female; Hormone Antagonists; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Pyridines; Random Allocation; Receptors, Endothelin; Receptors, Vasopressin; Tetrazoles; Vascular Resistance; Vasopressins

We studied whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during high epidural anesthesia when efferent sympathetic drive is diminished. On different days, six awake dogs underwent each of the following five interventions: blockade of vasopressin V(1a) receptors using [d(CH(2))(5)Tyr(Me(2))]AVP, (40 microg/kg) or endothelin receptors using tezosentan (3 mg/kg followed by 3 mg. kg(-1). h(-1)) with or without epidural anesthesia (1% lidocaine, intraindividual dose did not differ between experiments), and epidural saline (n = 5). The effects of endothelin- or vasopressin-receptor blockade were analyzed (means +/- SEM) and compared by an analysis of variance for repeated measures (paired Student's t-test, alpha-adjusted, P < 0.05). Vasopressin-receptor blockade decreased blood pressure (10 +/- 2 mm Hg) only in the presence of epidural anesthesia, whereas endothelin-receptor blockade reduced blood pressure both in the presence and absence of epidural anesthesia (12 +/- 3 versus 10 +/- 1 mm Hg). During baseline and each intervention, plasma concentrations of vasopressin and big-endothelin were measured and compared by a Wilcoxon's rank sum test; P < 0.05. Vasopressin concentrations increased during epidural anesthesia and after additional endothelin receptor blockade, but big-endothelin concentrations remained unchanged during each intervention. We conclude that vasopressin acts as a reserve system, as it stabilizes blood pressure specifically during epidural anesthesia, whereas the unchanged concentrations of big-endothelin indicate that the endothelin system is not specifically activated to support blood pressure during epidural anesthesia.. We studied in awake dogs whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during resting conditions and epidural anesthesia. Only vasopressin was specifically activated to support blood pressure during epidural anesthesia, whereas endothelin supported blood pressure to the same extent during epidural anesthesia and during resting conditions.

Topics: Anesthesia, Epidural; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Dogs; Endothelin Receptor Antagonists; Endothelins; Hormone Antagonists; Pyridines; Receptors, Endothelin; Receptors, Vasopressin; Tetrazoles; Vasopressins