Stimulatory Effect Of Phenylephrine Research Articles

Stimulatory effects of phenylephrine and 4β-phorbol-12β 13α-dibutyrate on phospholipase D activity in hypertrophied myocardium in a rat model*

Objectives: α1-Adrenoceptors play an important role in physiological and pathological cardiac hypertrophy. They trigger signaling through Gq-proteins, protein kinase C (PKC) and MAPK. It is still unclear whether, in development of hypertrophy, PKC is activated by second messengers (e.g. diacylglycerol=DAG) produced by phospholipase D (PLD) or C or by both. We studied the effect of aortic banding on PLD activated by the PKC stimulator phorbol ester (PBD) and α1-adrenoceptor agonist phenylephrine (PE).

Effect of crowding on corticosterone responses to central adrenergic stimulation.

The social stress of crowding for 3, 7 and 14 days considerably reduced the increase in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a beta-adrenergic agonist, on the 3rd and 7th days of crowding. The corticosterone response to clonidine, an alpha 2-adrenergic agonist, was significantly diminished only after 3 days of crowding and this reduction was paralleled by a significant decrease in hypothalamic histamine content. The stimulatory effect of phenylephrine, an alpha 1-adrenergic agonist, was not significantly changed by crowding stress. Social crowding stress caused almost total and persistent reduction in the hypothalamic-pituitary-adrenocortical (HPA) responsiveness to noradrenaline which stimulates the HPA axis via both alpha- and beta-adrenergic receptors.

Calcium dependence of phenylephrine-, endothelin-, and potassium chloride-stimulated atrial natriuretic factor secretion from long term primary neonatal rat atrial cardiocytes.

Since calcium is involved in both excitation-secretion and excitation-contraction coupling, it was of interest to evaluate its involvement in atrial natriuretic factor (ANF) release from atrial cardiocytes. In medium containing physiological levels of calcium (1.4 mM), the secretion of ANF from primary atrial cells was stimulated from 3- to 6-fold by a variety of agents including KCl, phenylephrine, and endothelium (ET). However, in medium containing 2 nM calcium, KCl was incapable of increasing ANF secretion above basal levels, while the stimulatory effects of phenylephrine and ET were only partially diminished. Nifedipine or verapamil could mimic the effects of the 2 nM calcium medium on KCl-, phenylephrine-, and ET-stimulated ANF secretion. Kinetic studies indicated that during the initial 5 min of ET-stimulated secretion the cells exhibited little requirement for extracellular calcium; however, the requirement was more apparent during the sustained secretion observed between 10 min and 2 h of secretagogue exposure. Additionally, the stimulation of ANF secretion by ET increased to a maximum of about 15-fold over basal by 10-min after ET application; subsequent to this time there was an apparent functional desensitization wherein the rate of secretion decreased by approximately 3-4-fold and remained at this level for the duration of secretagogue exposure up to 2 h. All forms of stimulated secretion could be inhibited through ionomycin-mediated depletion of intracellular calcium pools. Taken together, these results indicate that atrial cardiocytes require both extracellular and intracellular calcium to support maximal rates of stimulated ANF secretion, and that intracellular calcium pools may be used during the early phase of secretion, while the extracellular source of calcium may be important for the sustained phase of secretion.

Synergistic Interaction between Opioid Receptor Blockade and Alpha-Adrenergic Stimulation on Luteinizing Hormone-Releasing Hormone (LHRH) Secretion in vitro

The effects of opioid receptor blockade, alpha-adrenergic receptor stimulation and concomitant opioid blockade and adrenergic stimulation on LHRH neurosecretion was examined in tissue culture using perifused preoptic area-mediobasal hypothalamic (POA-MBH) explants. Blockade of opioid receptors using naloxone (NAL) resulted in increased (p less than 0.05) LHRH secretion from POA-MBH explants obtained from intact postpubertal female rats. After washout of the NAL-medium, basal release rate was reset to a lower baseline. Subsequent exposure of POA-MBH explants to phenylephrine (PHEN), an alpha-adrenergic agonist, resulted in a slight but statistically insignificant increase in LHRH release from adult explants. The attenuated response to PHEN may have been due to a sustained inhibition of LHRH release following the NAL exposure since PHEN not preceded by NAL resulted in a marked stimulation of LHRH release. In three separate experiments, the LHRH response in postpubertal rat explants to simultaneous PHEN and NAL was greater and more prolonged than the responses to either of the substances alone. This study demonstrates that the stimulatory effects of PHEN are much more profound in the presence of opioid receptor blockage. The observations of the stimulatory effects of PHEN and NAL potentiating each other also suggest that separate mechanisms of LHRH control by each class of neurotransmitter are present. Similar to the postpubertal rat explants, explants obtained from prepubertal rats increased LHRH release in response to NAL and showed a sustained inhibition of LHRH release following washout of NAL. Explants obtained from prepubertal rats also significantly increased LHRH release in response to PHEN.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of α-adrenergic stimuli in the control of rat renal ammoniagenesis

The effects of phenylephrine on renal ammoniagenesis and the involvement of Ca 2+ in phenylephrine action were investigated in isolated proximal fragments of rat-kidney tubules. Phenylephrine stimulated renal ammoniagenesis from 1 and 2 mM glutamine whereas no significant changes took place at a higher concentration of glutamine (20 mM). Stimulation of ammonia synthesis by phenylephrine was found to be linear with time and dose-dependent between 10 −9 and 10 −4 M. Phenylephrine-stimulated ammoniagenesis was blocked by phentolamine (10 μM) but not by propranolol (10 μM) confirming that the effect is mediated by α-adrenergic stimuli. No stimulatory effect of phenylephrine was observed in Ca 2+ depleted proximal tubule fragments, suggesting that Ca 2+ is required in this adrenergic response.

Alpha 1-adrenergic stimulation of hamster brown adipocyte respiration.

Respiration was increased approximately 5-fold with 0.05 microM norepinephrine and to a maximum of 10-fold by 0.30 microM norepinephrine. Prazosin, an alpha-adrenergic blocking agent highly selective for alpha 1-type receptors, partially inhibited the response to norepinephrine (0.05 microM) by 20-25% at a concentration of 0.10-1 microM. In contrast, when the stimulus for respiration was provided by isoproterenol or 3-isobutyl-1-methylxanthine, prazosin was without effect up to a concentration of 10 microM. Yohimbine, an alpha-adrenergic blocking drug preferential for alpha 2-receptors, did not influence norepinephrine-stimulated oxygen uptake. Respiration was increased two- to fourfold by phenylephrine or methoxamine, agents preferential for alpha 1-adrenergic receptors but not at all by clonidine, an agent preferential for alpha 2-adrenergic receptors. The stimulatory effect of phenylephrine on oxygen uptake was fully blocked by prazosin but not propranolol. Removal of extracellular calcium with ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid prevented phenylephrine stimulation of respiration but was without effect when isoproterenol was the stimulus. These results support the participation of alpha 1-adrenergic receptors in control of respiration and are consistent with the possibility that changes in cell calcium are intimately involved in this response.