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Angiotensin and the cardiac baroreflex response to phenylephrine.

1. In adult conscious sheep the pressor actions of infused angiotensin II were prevented by the concomitant intravenous infusions of sodium nitroprusside. The effect of such intravenous infusions of angiotensin II on the cardiac baroreflex response to transient rises in arterial pressure caused by intravenous phenylephrine was studied. 2. Intravenous infusion of angiotensin II caused a reduction in pulse interval in the absence of any change in arterial pressure. It also caused a reduction in baroreflex sensitivity measured by determining the relation between pulse interval and systolic pressure during the rise in pressure caused by injection of phenylephrine. 3. After administration of the converting enzyme inhibitor (captopril) the mean baroreflex sensitivity of 3 of 4 pregnant ewes increased. 4. It is concluded that high levels of angiotensin II can modify the cardiac baroreceptor reflex response so that the heart rate is inappropriately high for a given systolic pressure and that it reduces the sensitivity of the cardiac baroreflex response to transient changes in arterial pressure.

Angiotensin II↗

Effects of neuropeptide Y on the pressor responses to phenylephrine and to activation of the sympathetic nervous system in anaesthetized rats.

1. The effects of neuropeptide Y (NPY) on the pressor responses to intravenous injections of phenylephrine and to reflex activation of the sympathetic nervous system by stimulation of the sciatic nerve were examined in anaesthetized rats. 2. NPY (10-20 micrograms/kg) always potentiated the pressor response to exogenous phenylephrine (by a mean of 28.1 +/- 5.0%). The effect of the same dose of NPY on the pressor response to sciatic nerve stimulation was variable (sometimes inhibition, sometimes potentiation). 3. NPY appears to act by potentiating post-synaptic alpha-adrenoceptor-mediated vasoconstrictor effects. It may also inhibit noradrenaline release by a presynaptic action. Thus the net effect of NPY on sympathetic activation in vivo may depend on the balance between these two opposing actions.

Anesthesia↗

Effects of atrial natriuretic peptide on phenylephrine-induced renin release in dogs.

1. The effect of atrial natriuretic peptide (ANP) on alpha-adrenoceptor agonist-induced renin release was examined in the de-ennervated kidney of the anaesthetized dog pretreated with propranolol (1 mg/kg, intravenous). 2. Phenylephrine (50 ng/kg per min) infused into the renal artery increased the renal secretion rate of renin (RSR) without affecting systemic blood pressure or renal blood flow. 3. Although basal RSR was unaffected, the phenylephrine-induced increase in RSR was abolished during intrarenal arterial infusion of ANP (10 ng/kg per min). 4. The results suggests that exogenously administered ANP could suppress alpha-adrenoceptor-mediated renin release in the dog.

Animals↗

Analysis of the antagonism by prazosin of noradrenaline and phenylephrine induced contractions of the rat anococcygeus muscle.

1 Blockade of alpha-adrenoreceptors was analyzed with prazosin in the rat anococcygeus muscle contracted with noradrenaline (NA) and phenylephrine (PHE). 2 Prazosin (1.1 x 10(-8) - 8.8 x 10(-7)M) competitively blocked phenylephrine-induced contractions (pA2 = 8.93 +/- 0.04, slope = 0.85 +/- 0.07) whilst its antagonism of NA was non-competitive (pA2 = 8.45 +/- 0.04, slope = 0.46 +/- 0.03). 3 At higher concentrations, (1.76 x 10(-6) - 5.28 x 10(-6)M) prazosin competitively antagonized NA-induced contractions (pA2 = 7.58 +/- 0.11, slope = 0.93 +/- 0.09). 4 Phentolamine also reduced the effect of NA competitively (pA2 = 8.11 +/- 0.09, slope = 0.82 +/- 0.26). 5 It is concluded that low concentrations of prazosin selectively blocked an alpha 1-adrenoreceptor component of NA-mediated response whilst higher concentrations of prazosin non-selectively blocked both alpha 1- and alpha 2-adrenoreceptors.

Anal Canal↗

Glucagon and phenylephrine combination vs glucagon alone in experimental verapamil overdose.

OBJECTIVE: To evaluate glucagon and phenylephrine in combination as a treatment for the hemodynamic effects of verapamil overdose. METHODS: Pentobarbital-anesthetized and instrumented dogs were overdosed using a previously developed verapamil overdose model (15 mg/kg IV over 30 minutes). The animals were maintained and observed for 90 minutes or until death. Cardiac output (CO), heart rate (HR), and mean arterial pressure (MAP) were monitored. Following the 30-minute verapamil infusion (toxicity), the control animals received no treatment; the glucagon animals received a 5-mg glucagon bolus and a drip of 5 mg/90 minutes; and the glucagon/phenylephrine animals received the same glucagon therapy plus a phenylephrine drip titrated to 180 micrograms/min over 15 minutes. The groups were compared using analysis of variance: the experimental variables were group and time; the response variables were changes from toxicity for the hemodynamic parameters. Post-hoc comparisons were done with alpha set at 0.05. RESULTS: A significant change in CO was seen in the glucagon group (delta = 2.6 L/min) and the glucagon/phenylephrine group (delta = 1.9 L/min) compared with the control group (delta = 0.8 L/min). The change in CO was significantly larger for the glucagon animals compared with the glucagon/phenylephrine animals. The change in MAP for the glucagon/phenylephrine group (delta = 24 mm Hg) was significant compared with the control group (delta = 14 mm Hg). The MAP change for the glucagon group (delta = 19 mm Hg) was not significantly different from that of either the control or the glucagon/phenylephrine group. The change in glucagon HR (delta = 6 beats/min) was significant compared with the control group (delta = -4 beats/min) and the glucagon/phenylephrine group (delta = -4 beats/min). CONCLUSION: The glucagon/phenylephrine therapy improved MAP compared with the control, but reduced CO and HR compared with glucagon alone. Glucagon/phenylephrine therapy is not as effective as glucagon alone in reversing the hemodynamic effects of experimental verapamil overdose.

Adrenergic alpha-Agonists↗

The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants.

In this prospective study, microdrops (mean drop volume 5.6 microl) and commercially available standard drops (mean drop volume 35.4 microl) of cyclopentolate, phenylephrine and tropicamide's clinical efficacy and systemic side effects were compared. Sixty-one infants requiring diagnostic pupil dilatation were studied for pupillary diameter, systemic blood pressure, heart rate and skin flushing changes related to the instillation of mydriatic drops. Both microdrops and standard drops of the drugs produced significant increase in pupillary diameter compared with the baseline (p<0.01). In cyclopentolate and phenylephrine groups, there was no significant pupillary diameter changes between microdrops and standard drops (p>0.05). Mean blood pressure increased significantly in infants given standard drops. There was no significant change in the group that was given microdrops. In our opinion, reduced volume of mydriatics can prevent possible side effects.

Administration, Topical↗

Regional cerebral blood flow in acute hypertension induced by adrenaline, noradrenaline and phenylephrine in the conscious rat.

Hypertension was induced in conscious rats by intravenous infusion of phenylephrine (3, 6 or 12 micrograms kg-1 min-1), noradrenaline (3 micrograms min-1) or adrenaline (3 micrograms kg-1 min-1). Local cerebral blood flow was measured autoradiographically in 24 defined brain structures using [14C]iodoantipyrine as the diffusible tracer. The mean arterial pressure induced by adrenaline, noradrenaline and the two higher doses of phenylephrine was 158-168 mmHg with no significant differences between the groups. Only adrenaline significantly increased local cerebral blood flow in nine of the 24 structures studied. The smaller capacity for autoregulation after adrenaline compared with other drugs might be related to a beta-adrenoreceptor-stimulating effect.

Animals↗

A cross-over study of the cycloplegic effects of a single topical application of cyclopentolate-phenylephrine and routine atropinization for 3.5 days.

Static refraction in children after the topical instillation of atropine twice a day during 3.5 days was compared with the refraction after a single instillation of one drop of 0.85% cyclopentolate + 1.5% phenylephrine in a randomized cross-over study. Atropine eye drops were applied by the parents at home, while the combination drop was applied by personnel at the eye clinic. Refraction was determined by retinoscopy in 40 children (3-6 years) in a single blind manner. No statistically significant difference in cycloplegic effect was found between the 2 methods. The results imply that in clinical practice a single instillation of a combination of 0.85% cyclopentolate and 1.5% phenylephrine can be substituted for conventional "full" atropinization during 3.5 days.

Accommodation, Ocular↗

Exfoliation syndrome and the effect of phenylephrine and pilocarpine on pupil size.

The horizontal diameter of the pupil was measured on 20 eyes with exfoliation syndrome and 20 control eyes before and after the instillation of 10% phenylephrine and 4% pilocarpine eye drops. Pupil dilation induced by topical application of the alpha 1 adrenoceptor agonist phenylephrine was significantly smaller in eyes with exfoliation syndrome compared to controls. The cholinergic agonist pilocarpine decreased pupil diameter and this effect was significantly less in cases with exfoliation syndrome. We conclude from these data that the pharmacological response to both adrenergic and cholinergic stimulation is weaker in eyes with exfoliation syndrome compared to controls.

Aged↗

Beta-adrenoceptor stimulating effects of phenylephrine and noradrenaline in the rat pulmonary vascular bed.

The effects of phenylephrine and noradrenaline have been investigated on the perfusion pressure of the rat isolated lung. Both drugs (0.3-30 micrograms) produced a dose-dependent decrease in perfusion pressure elevated by 20 mM KCl, which was reversed to a dose-dependent increase after addition of propranolol (1 x 10(-7) M) to the perfusion fluid. Increments due to both agonists in the presence of propranolol were antagonized by prazosin (1 x 10(-6) M). Propranolol, but not prazosin, elevated the basal perfusion pressure. The results indicate that phenylephrine and noradrenaline are more effective in stimulating beta-adrenoceptors than alpha-adrenoceptors in the rat pulmonary vascular bed and that beta-adrenoceptors may regulate the vascular tone of the rat pulmonary circulation.

Adrenergic beta-Agonists↗

Effects of isoprenaline plus phenylephrine by pressurized aerosol on blood gases, ventilation, and perfusion in chronic obstructive lung disease.

The effects of a combined isoprenaline-phenylephrine inhalant in chronic obstructive lung disease were assessed in 23 patients. Significant changes occurred in blood gas tensions after inhalation, together with an overall improvement in ventilation/perfusion ratios. Cardiac output and physiological shunt were not significantly increased. Hence the addition of phenylephrine probably prevents the increase of hypoxaemia which may result from the disproportionate ventilation/perfusion ratio produced by sympathomimetics or xanthines used alone. The combination aerosol has a satisfactory bronchodilator effect, and is additionally safe if used by a severely hypoxic patient unaware of the seriousness of his condition.

Adult↗

Effects of the adrenergic nervous system on training-induced cardiac enlargement, and on the intrinsic rate and phenylephrine sensitivity of isolated rat atria.

Atria isolated from rats after 6 to 7 weeks running training or swim training in water at 30 degrees C beat at a slower rate than did the atria from sedentary control animals. If the rats received noradrenaline injections with each running session their atrial rate was even lower, while propranolol injections did not lead to lower intrinsic atrial rate. Repeated noradrenaline or propranolol injections alone or swim training in warm water (38 degrees C) did not result in altered atrial rate. A plot of the intrinsic atrial rate against heart weight yielded a significant (r = -0.803) negative relationship (y = 311 - 0.91 x). Swim training in cold water, or chronic noradrenaline injections led to a lessened sensitivity of isolated atria to phenylephrine while chronic beta blockade tended to increase the sensitivity. The results suggest that an intense, although transient, cardiac stimulation, typical of the combined action of running training and noradrenaline injections, results in a lower intrinsic atrial rate and greater cardiac enlargement, while a more sustained type of cardiac stimulation, as produced typically by repeated injections of noradrenaline, leads to less sensitivity to phenylephrine.

Adaptation, Physiological↗

Phenylephrine and endothelin differentially stimulate cardiac PI hydrolysis and ANF expression.

In ventricular myocytes, phenylephrine (PE) and endothelin (ET) stimulate phosphoinositide (PI) hydrolysis, cell growth, and expression of several genes [e.g., atrial natriuretic factor (ANF)] often associated with cardiac hypertrophy. In this study the production of inositol monophosphate (InsP) and diglyceride (DG), both products of PI hydrolysis, and ANF were monitored during long-term exposure (up to 72 h) to PE or ET. For PE, InsP production increased and continued unabated throughout the time course; DG levels also increased and remained elevated, and similar rates of ANF production were observed from 24 to 72 h. For ET, the initial InsP and DG responses equaled those to PE, but diminished by 24 h. ET-stimulated ANF production equaled the PE response at 24 h but subsided by 72 h. Adding PE to cells previously desensitized to ET elicited maximal InsP formation, indicating the desensitization was ET specific. These data emphasize that while phenylephrine and endothelin have similar initial effects on cardiac second messenger production and ANF expression, hormonally specific patterns develop over extended periods of exposure.

Animals↗

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep.

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial PO(2) (PaO(2)) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 microg. kg(-1). min(-1)) or the alpha(1)-adrenergic agonist phenylephrine (6.5 microg. kg(-1). min(-1)) into the umbilical vein or during hypoxemia (fetal Pa(O(2)) reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an alpha(1)-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.

Adrenergic alpha-Agonists↗

NG-nitro-L-arginine and phenylephrine have similar effects on the vascular waterfall in the canine hindlimb.

Hindlimb pressure-flow relationships are well characterized by modeling a vascular waterfall at the arteriolar level. Under these conditions, Q = (Pper - Pcrit)/Rart, where Q is blood flow, Pper is perfusion pressure, Pcrit is waterfall pressure, and Rart is the resistance upstream from the waterfall. To determine the effects of endothelium-derived relaxing factor (EDRF) on Pcrit, Rart, and venous resistance (Rv), we varied Pper in the canine hindlimb between 100 and 200 mmHg before and after NG-nitro-L-arginine infusion (L-NNA, an inhibitor of EDRF synthesis). Before L-NNA, Pcrit increased with increasing Pper. After L-NNA, Pcrit was higher at each Pper, and the increase in Pcrit with increases in Pper was greater than under control conditions. In contrast to Pcrit, Rart decreased with increasing Pper before L-NNA. After L-NNA, Rart was higher at each Pper and no longer decreased with increasing Pper. Rv was not affected by Pper under control conditions but decreased with increasing Pper after L-NNA. The pressure in the small venules at each Pper decreased after L-NNA. In a second group of animals, we infused phenylephrine to control for increased tone produced by L-NNA. Results were similar to those seen with L-NNA. In conclusion, blocking EDRF synthesis increases both Pcrit and Rart, but the same response was also obtained with phenylephrine.

Animals↗

Impaired reactivity of rat aorta to phenylephrine and KCl after prolonged hypoxia: role of the endothelium.

The hemodynamic response to reductions in systemic oxygen availability serves to redistribute blood flow and maintain vital organ function. The efficacy of this response depends on the degree to which hypoxia alters the function of the vascular tissues themselves. In this study we have evaluated these effects in rats exposed to 10% oxygen for 0 (control), 12, and 48 h and for 48 h followed by 12 h of normoxic recovery. In aortic segments from each group, the cumulative concentration response relationships were constructed for phenylephrine and KCl. Maximum tension generated during activation by these agents was reduced after both 12 and 48 h of hypoxic exposure. After 48 h of hypoxia, the maximum tension during activation by phenylephrine was 0.46 +/- 0.04 vs. 1.31 +/- 0. 09 g/mg dry wt for the control group (P < 0.05 for difference). The maximum tension during activation by KCl was similarly affected (0. 32 +/- 0.02 vs. 0.98 +/- 0.06 g/mg dry wt, 48 h of hypoxia vs. control, respectively; P < 0.05 for difference). Exposure to hypoxia did not alter the EC50 for either agent. Twelve hours of normoxic recovery did not fully restore contractility after 48 h of hypoxia. In aortic rings from control rats, endothelial removal enhanced contraction, whereas, in rings from rats exposed to hypoxia, removal of the endothelium was associated with a decrease in maximum tension. Prolonged exposure to hypoxia results in impairment of systemic arterial smooth muscle contractility. This is partly compensated by the release of vasoconstricting substances from the endothelium.

Acetylcholine↗

Effect of chronic exposure to cold on vascular responsiveness to phenylephrine and angiotensin II.

Chronic exposure of rats to cold (5 degrees C, 3-4 weeks) results in the development of hypertension. To assess potential mechanisms by which this may occur, the vascular responsiveness to administration of phenylephrine (an alpha-adrenergic agonist) and angiotensin II (AII) was studied in unanesthetized rats at 1, 3 and 5 weeks of exposure to cold (5 degrees C). Vascular responsiveness to intravenous administration of graded doses of phenylephrine was reduced in cold-treated rats, the earliest effect being observed within 1 week of exposure. With respect to AII, vascular responsiveness to graded intravenous doses increased maximally within 1 week of exposure to cold and returned toward the level of the control group at 3 weeks. After 5 weeks of exposure to cold, it had returned to the level of the control group. These results suggest that vascular responsiveness to alpha-adrenergic stimulation appears to be directed toward prevention of an elevation of blood pressure in cold-treated rats. In contrast, vascular responsiveness to administration of AII is increased during the first 3 weeks of exposure to cold, at a time when plasma renin activity is also increased, and may thus play an important role in the initiation of cold-induced elevation of blood pressure.

Angiotensin II↗

Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatic mechanisms.

BACKGROUND: Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine. METHODS AND RESULTS: Eight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6 micrograms.kg-1.min-1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P < .05 using repeated-measures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P < .05 for % delta of forearm versus % delta of finger readings during the 0.4 microgram.kg-1.min-1 infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 microgram.kg-1.min-1 infusion. CONCLUSIONS: As expected, laser Doppler readings at the finger decreased during infusion of an alpha 1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4 microgram.kg-1.min-1 infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.

Blood Flow Velocity↗