Bolus Of Norepinephrine Research Articles

Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.

Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.

Renal hemodynamic changes during serial seizures in rats

Renal blood flow (RBF) and mean arterial blood pressure (MABP) were measured during serially induced seizures in anesthetized paralyzed rats to investigate possible alterations in hemodynamic responses during experimental status epilepticus. During initial seizures, MABP increased from 143 to 193 mmHg, and RBF decreased from 4.8 to 1.5 ml/min. In contrast, MABP fell from 124 to 100 mmHg and RBF dropped from 3.6 to 2.8 ml/min during late seizures. The large decreases in RBF during initial seizures were blocked by renal denervation or bilateral adrenalectomy. During the period of late seizures, both the increase in MABP and the decrease in RBF in response to intravenous boluses of norepinephrine fell to 55% of the preseizure value. Our data indicate that the marked decreases in RBF during early seizures can be mediated by either the renal nerves or the adrenal glands. Furthermore, decreased sensitivity of the vasculature to norepinephrine likely contributes to the diminution of both MABP and RBF responses during later seizures.

Unmasking sensitive alpha 2-adrenoceptor-mediated renal vasoconstriction in conscious rats.

Renal vascular reactivity to intrarenal arterial boluses of norepinephrine (NE), phenylephrine (PHE; alpha 1-agonist), and guanabenz (GBZ; alpha 2-agonist) was assessed in conscious, freely moving, chronically instrumented, normotensive Wistar rats. Dose-response curves (DRCs) were obtained in the absence and cumulative presence of propranolol (PROP; beta-antagonist), corynanthine (CORY; alpha 1-antagonist) and idazoxan (IDX; alpha 2-antagonist) to estimate effective dosages (ED) required for 15 and 75% peak reductions in renal blood flow. The PHE DRC had a short shallow ED15 region, but was primarily linear with a steep slope. The GBZ DRC had a shallow slope. The NE DRC had a prolonged shallow phase in the ED15 region and a steep slope in the ED75 region. PROP had no effect on the DRCs. CORY caused a parallel rightward shift of the PHE DRC and had no effect on the GBZ DRC. After CORY, the shallow ED15 portion of the NE DRC was even more pronounced with a slope now identical to that of the GBZ DRC, whereas the ED75 region of the NE DRC was shifted rightward like the PHE DRC. IDX preferentially antagonized the ED15 regions of the GBZ and NE DRCs. In a second group of rats, the alpha 2-adrenoceptor antagonist, rauwolscine, was administered following base-line DRCs to demonstrate rightward shifts of the NE and GBZ DRCs when PHE DRCs remained unaffected. Therefore, when boluses of NE are injected into the rat kidney, the vasoconstrictive responses are a result of the activation of both alpha 1- and alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine and Norepinephrine Increase Venous Return by Stimulating α and β Adrenoceptors in the Dog

The cardiopulmonary bypass technique was used to compare the effects of dopamine and norepinephrine on venous return, and to identify the adrenoceptors involved in the responses. Intraarterial boluses of dopamine and norepinephrine produced similar increases in mean arterial pressure and similar increases in venous return, but dopamine required 10-30 x larger doses than norepinephrine to produce the same effect. Phenoxybenzamine virtually abolished the venous responses to the lowest doses of both agonists and diminished the venous responses to larger doses. Propranolol had little or no effect on venous responses to the low doses but substantially diminished the responses to larger doses. These results indicate that the increase in venous return produced by dopamine or norepinephrine involves both alpha and beta adrenoceptors. To determine whether the beta adrenoceptor belonged to subtype beta 1, the "selective" beta 2 agonist, salbutamol, was used. The reported affinity of salbutamol in dogs for arterial beta 2 receptors is fivefold greater than that for cardiac beta 1 receptors. However, the dose-response curves of salbutamol on the venous and arterial systems overlapped, indicating that the increase in venous return represents a combination of properties common to both beta 1 and beta 2 adrenoceptors.

Neural stimulation of gluconeogenesis in isolated pyruvate-perfused rat kidneys.

To estimate peritubular norepinephrine concentration during renal nerve stimulation, we compared gluconeogenic responses in isolated pyruvate-perfused rat kidneys with electrical nerve stimulation and exogenous norepinephrine. During 2 and 4 Hz stimulation, venous norepinephrine was 1.7 +/- 0.4 and 2.7 +/- 0.9 nmol/L, respectively. Intra-arterial norepinephrine infusion of 60 pmol/min for 20 min (an amount corresponding to that released during 4 Hz stimulation) resulted in venous norepinephrine levels of 3.6 +/- 0.6 nmol/L. Electrical stimuli (1, 2, and 4 Hz) sustained increases in vascular resistance of 2, 5, and 11% during 20 min of stimulation, while the norepinephrine infusion increased resistance gradually by 8% and a bolus (12.5 nmol/L) transiently increased resistance by 2%. All electrical and norepinephrine interventions, except 1 Hz, decreased fractional Cl excretion. Decreased glomerular filtration rate was observed only during 4 Hz stimulation. Gluconeogenesis transiently increased during stimulation at 2 or 4 Hz (12% (p = 0.056) and 15% (p = 0.028]. The 5% increase in gluconeogenesis during norepinephrine infusion did not differ from the increase during 4 Hz stimulation (p = 0.45). An exogenous norepinephrine bolus (12.5 nmol/L) increased gluconeogenesis 60% for 15 min, four time more than the response to 4 Hz nerve stimulation (p = 0.012). Therefore, we conclude that nerve stimulation sufficient to produce sustained vasoconstriction and antinatriuresis raised norepinephrine concentration less than 12 nmol/L on the peritubular surface of the S1 proximal tubule, thus accounting for the small gluconeogenic response.

The direct and amplifying effects of serotonin are increased with age in the isolated perfused kidney of Wistar and spontaneously hypertensive rats.

Isolated kidneys of Wistar rats and spontaneously hypertensive rats (SHR) were perfused with Tyrode's solution. In 2- and 6-month old SHR, the maximal increase in perfusion pressure caused by norepinephrine was higher than in 2- and 6-month old Wistar rats, but the sensitivity, as judged from the dose of the agonist required to reach 50% of the maximal response was the same. Both the maximal response and the sensitivity to serotonin were significantly augmented in 6-month old SHR and Wistar rats when compared to the young animals. This hypersensitivity was more pronounced in SHR than in Wistar rats. Infusion of serotonin potentiated the vasoconstriction induced by a bolus of norepinephrine. This amplification, due to activation of S2-serotonergic receptors, was more pronounced in the old animals. No amplification occurred when norepinephrine was infused instead of serotonin. Tachyphylaxis to the amplifying effect of serotonin was observed and was less pronounced in kidneys from old than from young animals. The amplifying effect of serotonin was inhibited by ketanserin at concentrations which did not, or only moderately, inhibit the response to norepinephrine.

Effect of physical training on norepinephrine turnover in tissues of normal and diabetic rats

This study was designed to examine the influence of physical training on the norepinephrine turnover rate in heart, pancreas, liver, and gastrocnemius muscles of normal and diabetic male rats at rest. Diabetes was induced with the IV injection of streptozotocin (45 mg/kg) and physical training was done on a treadmill according to a ten-week program. Norepinephrine turnover rate of tissues was estimated by following over time the decay in the specific activity of norepinephrine after a single IV bolus of tritiated norepinephrine (30 μCi/kg). Plasma glucose, insulin, and glucagon levels were also measured at the time of death. Although training caused a reduction in the plasma glucose values of diabetic rats, no changes in norepinephrine turnover rate were observed after the conditioning program. On the other hand, diabetes was associated with a significant 30% to 40% decrease in the pancreatic norepinephrine turnover rate. It is concluded that the beneficial effects of physical training on diabetes mellitus cannot be explained by adaptive changes in the sympathetic nervous system activity and that further work will be necessary to elucidate the mechanism whereby streptozotocin diabetes diminishes the pancreatic norepinephrine turnover.

Uptake and metabolism of norepinephrine in isolated perfused fetal, newborn and adult rabbit lungs

We compared the ability of isolated perfused lungs from previable, 26-day gestation, fetal rabbits; newborn rabbits (within 12 hours of birth) and 3 month old adult rabbits to metabolize a 20-second bolus of norepinephrine (NE). The concentration of NE infused was much below the Km for the NE uptake process to assure first order uptake kinetics. At these low concentrations no vasoactivity was observed. The retention time of a vascular marker dye was monitored as an index of pulmonary vascular surface area. In all three sizes of lungs perfusate flow was adjusted to produce an approximately 7 second dye retention time. At these flows adult and newborn lungs inactivate about 50 to 60 percent of the infused NE. In contrast, fetal rabbit lungs inactivate about 80 percent of the infused NE. We conclude that circulating NE is most avidly taken up and metabolized during fetal lung development. The physiologic significance of this fetal NE inactivation remains unknown.