Bbeta-adrenergic receptor kinase-1 levels in catecholamine-induced myocardial hypertrophy: regulation by beta- but not alpha1-adrenergic stimulation.

Pressure overload ventricular hypertrophy is accompanied by dysfunctional beta-adrenergic receptor signaling due to increased levels of the beta-adrenergic receptor kinase-1, which phosphorylates and desensitizes beta-adrenergic receptors. In this study, we examined whether increased beta-adrenergic receptor kinase 1 expression is associated with myocardial hypertrophy induced by adrenergic stimulation. With use of implanted mini-osmotic pumps, we treated mice with isoproterenol, phenylephrine, or vehicle to distinguish between alpha1- and beta-adrenergic stimulation. Both treatments resulted in cardiac hypertrophy, but only isoproterenol induced significant increases in beta-adrenergic receptor kinase-1 protein levels and activity. Similarly, in isolated adult rat cardiac myocytes, 24 hours of isoproterenol stimulation resulted in a significant 2.8-fold increase in beta-adrenergic receptor kinase-1 protein levels, whereas 24 hours of phenylephrine treatment did not alter beta-adrenergic receptor kinase-1 expression. Our results indicate that increased beta-adrenergic receptor kinase-1 is not invariably associated with myocardial hypertrophy but apparently is controlled by the state of beta-adrenergic receptor activation.

Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P-CV) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P-CV during a total occlusion of blood flow from the heart.Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 mu g kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P-CV, whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P-CV and MCFP. Thus, nitric oxide seems to affect venous tone.

Food restriction impairs myocardial inotropic response to calcium and beta-adrenergic stimulation in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cholinergic and adrenergic stimulation of the subfornical organ on water intake

Cholinergic and adrenergic agonists and antagonists were injected directly into the subfornical organ (SFO), via implanted cannulae, and the volume of water ingested was recorded over a period of 1 hour after injection. Application of 2 nmol carbachol caused intense water intake in 100% of the animals (8.78±0.61 ml), with a very short intake latency. When the 2 nmol carbachol dose was preceded by increased doses of atropine, a progressive reduction in water intake was observed, with complete blockage of the thirst-inducing response to carbachol at the 20 nmol dose level with atropine. Followed by several doses of hexamethonium, the water intake caused by application of 2 nmol carbachol was reduced, although the response was not totally blocked. Injection of 80 nmol of nicotine had a significant thirst-inducing inducing effect in 50% of the animals studied (1.06±0.18 ml) and increase in water intake was further reduced by application of increased doses of hexamethonium. Raising the dose levels of noradrenaline into th SFO caused an increase in water intake although to a lesser degree than was observed after carbachol injection. When the 40 nmol dose of noradrenaline was preceded by increased doses of propranolol (5 to 40 nmol), there was a gradual reduction in water intake, with total blockage at the 40 nmol dose. Application of phentolamine in doses of 10 to 80 nmol caused no reduction in water intake after 40 nmol of noradrenaline. Application of isoproterenol at doses from 20 to 160 nmol into the SFO caused a dosedependent increase in water intake which was blocked by previous applications of propranolol. These results support the hypothesis that the water intake caused by chemical stimulation of the SFO is mainly due to muscarinic cholinergic receptors, although the influence of nicotinic receptors or participation of adrenergic mediation should not be ruled out. © 1984.

Effect of adrenergic stimulation of the amygdaloid complex on water intake

The effect of noradrenaline, isoproterenol, phentolamine and propranolol, injected into the basolateral nuclei of the amygdala on water intake, was investigated in male Holtzman rats. The injection of noradrenaline (40 nmol) into the amygdaloid complex (AC) of satiated rats produced no change in water intake (0.05 ± 0.03 ml/1 hour). The injection of isoproterenol (40 nmol) produced an increase in water intake in sedated rats (1.93 ± 0.23 ml/1 hour). Noradrenaline injected into the AC produced a decrease in water intake in deprived rats (0.40 ± 0.19 ml/1 hour). The injection of isoproterenol into the AC of deprived rats produced no change in water intake in comparison with control (11.65 ± 1.02 and 10.92 ± 0.88 ml/1 hour, respectively). When compared with control values, phentolamine injected prior to noradrenaline blocked the inhibitory effect of noradrenaline on water intake in deprived rats (10.40 ± 1.31 ml/1 hour). Propranolol blocked the effect of isoproterenol in satiated rats (0.85 ± 0.49 ml/1 hour) and also blocked the water intake induced by deprivation (0.53 ± 0.38 ml/1 hour). In satiated and deprived animals the injection of phentolamine before hexamethonium blocked the inhibitory effect of hexamethonium on water intake. In satiated animals, when hexamethonium was injected alone, water intake was 0.39 ± 0.25 ml/1 hour and when hexamethonium was injected with phentolamine, water intake was 1.04 ± 0.3 ml/1 hour. In deprived animals, hexamethonium alone blocked water intake (0.40 ± 0.17 ml/1 hour) and when injected with phentolamine it elicited an intake of 9.7 ± 1.8 ml/1 hour. these results clearly demonstrate the participation of catecholaminergic receptors of the AC in the regulation of water intake.