Norepinephrine Dose-response Curves Research Articles

α-adrenoceptor occupancy by N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) in rat vas deferens

The effects of N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) on α 1- and α 2-adrenoceptors were examined in the isolated rat vas deferens. The active species of DMPEA was the corresponding ethyleniminium ion, which forms in the biophase, since pretreatment of tissues with sodium thiosulphate completely prevented the DMPEA-induced inhibition at α 1- and α 2-adrenoceptors. DMPEA was approximately 42-fold more potent in inhibiting α 2-adrenoceptors than it was in inhibiting α 1-adrenoceptors. The antagonism of both receptor types was reversible since washing of the tissues after incubation with DMPEA brought the agonist dose-response curve back to the control value. At α 1-adrenoceptors, DMPEA displaced the noradrenaline dose-response curve to the right and concomitantly depressed the maximum response, effects which are consistent with a non-competitive mechanism of action. At α 2-adrenoceptors, DMPEA caused a parallel shift of the clonidine or noradrenaline dose-response curve to the right in field-stimulated prostatic portions of the rat vas deferens. The antagonism appeared to be competitive at low concentrations, whereas the shift of the clonidine dose-response curve at higher concentrations became overproportional to the DMPEA concentration. A combination of DMPEA with idazoxan produced a less-than-additive shift of the dose-response curve for clonidine, indicating that these antagonists do not bind to the same site.

Bioassay by cross-perfusion for circulating inotropic factor in hypertension

To study inotropic effects of blood from one-kidney, one-clip (1K,1C) rats with early (less than 7 days) or chronic (greater than 4 wk) benign hypertension, we assessed arteriolar resistance and norepinephrine (NE) responses in vascularly isolated, innervated assay hindlimb vascular beds of alpha-chloralose-anesthetized, normal male recipient rats. Hindlimbs were cross-perfused (2 ml/min) with blood from anesthetized donor rats with limb outflow returned to the donor rat. Perfusion pressure was monitored. Complete NE (injected intra-arterially) dose-response curves in limbs perfused with donor blood from nine early 1K,1C rats, compared with nine appropriate normotensive control donor rats, indicated unchanged thresholds, 50% effective doses, and maximal responses. Curves in limbs perfused with blood from 10 chronic 1K,1C, compared with 10 appropriate controls, suggested small (P less than 0.02) leftward shifts. Decreases (P less than 0.01) in maximal responses were also observed. Limb resting resistance and minimal resistance (sodium nitroprusside) did not rise, even after 4-5 h of cross-perfusion. These results provide no evidence in early 1K,1C and little evidence in chronic 1K,1C that humoral factors, including ouabainlike inhibitors, evoke physiologically significant inotropic effects in arterioles in vivo.

Changes in Sensitivity of the Rat Stomach Fundus to Various Drugs in Streptozotocin-Induced Diabetic Rats

The changes in sensitivity of the rat stomach fundus to acetylcholine (ACh), norepinephrine (NE), isoproterenol (ISO) and to vasoactive intestinal peptide (VIP) were examined in control rats and in streptozotocin (STZ)-induced diabetic rats. The dose-response curves for drugs were constructed 8 weeks after treatment with STZ. The dose-response curve for ACh in diabetic rats was shifted to the left as compared to the control curve, whereas the dose-response curves for NE, ISO and VIP were shifted to the right. These results suggest that functional changes in the autonomic nervous systems of the rat stomach fundus may occur in STZ-induced diabetic rats.

Changes in sensitivity of the rat stomach fundus to various drugs in streptozotocin-induced diabetic rats.

The changes in sensitivity of the rat stomach fundus to acetylcholine (ACh), norepinephrine (NE), isoproterenol (ISO) and to vasoactive intestinal peptide (VIP) were examined in control rats and in streptozotocin (STZ)-induced diabetic rats. The dose-response curves for drugs were constructed 8 weeks after treatment with STZ. The dose-response curve for ACh in diabetic rats was shifted to the left as compared to the control curve, whereas the dose-response curves for NE, ISO and VIP were shifted to the right. These results suggest that functional changes in the autonomic nervous systems of the rat stomach fundus may occur in STZ-induced diabetic rats.

Cardiac effects of ketanserin, a serotonin antagonist--electrophysiological examinations as a part of toxicity studies.

Cardiac effects of ketanserin were examined mainly electrophysiologically with using rat and guinea pig heart muscle preparations. 10(-6)M ketanserin slightly antagonized the positive chronotropic but not inotropic action of serotonin in spontaneously beating guinea pig atria. Ketanserin, only at the concentration as high as 10(-4)M, produced slight rightward shift of the positive chronotropic but not inotropic dose-response curves for norepinephrine in guinea pig atria. In both rat and guinea pig atria, ketanserin per se produced negative chronotropic effect and slight prolongation of action potential duration (APD) at high concentrations, 0.1 or 0.3 mg/ml. In guinea pig ventricular preparation, 1 mg/ml of ketanserin did not affect the rate of rise of the action potential (+Vmax), action potential amplitude and APD. In rat ventricular free wall preparations, 1 mg/ml of ketanserin produced slight increase in APD without affecting the other action potential parameters. In rat ventricular papillary muscle and septum preparations, 0.3 mg/ml of ketanserin tended to produce a decrease in +Vmax and an increase in APD. However, since these changes were produced only at extremely high concentrations and slight in degree, it was concluded that ketanserin does not produce electrophysiological side effects of clinical relevance.

Effects of prazosin and indomethacin on the alpha-adrenergic stimulation of rabbit myometrium.

The effect of norepinephrine (NE) stimulation of near-term pregnant rabbit myometrium was studied by comparing cumulative dose-response curves for NE and NE with prazosin or indomethacin. Prazosin blocked the stimulatory effects of NE. Indomethacin pretreatment resulted in attenuation, but not suppression of contractile activity. Myometrial activity was associated with a progressive increase in the synthesis of prostaglandin (PG) F2 alpha. Our observations suggest that alpha-adrenergic agonists have some myometrial stimulating effect independent of PG production.

The vascular Na+-K+ pump in experimental hypertension.

We assessed the role of putative circulating ouabainlike factor(s) on in vivo arteriolar function in rats with very early (less than 7 days; mean, 3 days) and chronic (greater than 4 weeks) benign, one-kidney, one clip (1K1C) hypertension. Thus, we measured vascular responses in vasodilated (nitroprusside or adenosine), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized 1K1C rats perfused with their own blood at 1 ml/min. Complete norepinephrine dose-response curves in 8 rats with chronic and 28 with early 1K1C hypertension, compared with appropriate normotensive control rats, showed unchanged thresholds and ED50 values. Magnitude of ouabain-induced leftward shifts of the norepinephrine dose-response curve in 18 rats with chronic and 21 with early 1K1C hypertension, compared with appropriate normotensive control rats, was unchanged. Blockade of neural uptake of norepinephrine by desimipramine (10(-7) M) in 8 1K1C rats did not alter these results. These findings provide no evidence in this form and these stages of hypertension that humoral ouabainlike inhibitors of the Na+-K+ pump evoke physiologically significant inotropic effects in arterioles in vivo. It is possible, however, that induction of vascular Na+-K+-adenosine triphosphatase by circulating inhibitors modified the vascular responses to norepinephrine and ouabain in these rats.

Length-dependent sensitivity of vascular smooth muscle in normotensive and hypertensive animals.

Ring segments were obtained from the aorta of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WST) rats and from the anterior tibial artery of normotensive and hypertensive dogs. Norepinephrine dose-response curves were generated at lengths relative to that for maximum force (Lmax) and at a specific preload (in grams). The doses of stimulus necessary to elicit 10 and 50% maximum force of contraction (ED10 and ED50) are greater at lengths less than Lmax than at Lmax for all groups. When SHR rings are compared with WKY or WST rings, ED10 or ED50 is the same at either length. The same result was found in comparing normal and hypertensive dogs. ED10 and ED50 from hypertensive groups were the same as their respective control groups when compared at the same preload. We conclude that sensitivity of the rat aorta and dog anterior tibial artery to norepinephrine depends on muscle length, this relationship is not altered in hypertension, and the conclusion on sensitivity in hypertension is the same for excised rings compared at the same length or at the same preload. Contractility (active stress) was lower (rats) or the same (dogs) but thickness was greater in the hypertensive groups than in their controls. The results show that a change in the vessel wall that can cause increased flow resistance and pressure is not in sensitivity or contractility but in wall thickness. Apparent differences in sensitivity from normal and hypertensive animals can be explained by an unchanged length-dependent sensitivity. The results also show that differences in body weight will affect a comparison of wall tension but not of sensitivity.

Adrenergic dysfunction in hereditary adult-onset leukodystrophy.

We studied the pressor response to norepinephrine infusion in patients with an autosomal dominant adult-onset leukodystrophy. We also examined cardiovascular and catecholamine responses to insulin-induced hypoglycemia. A parallel shift to the left of the norepinephrine dose response curve, in conjunction with low baseline plasma norepinephrine levels, was consistent with denervation supersensitivity, suggesting a distal lesion of sympathetic noradrenergic neurons. Absence of the epinephrine response to insulin-induced hypoglycemia indicated that autonomic neuropathy was attended by severe adrenal medullary dysfunction.

Difference in the potency of α2‐adrenoceptor agonists and antagonists between the pithed rabbit and rat

The subtypes of alpha-adrenoceptors which mediate pressor responses to sympathomimetic agonists or to nerve stimulation in pithed rabbits have been classified according to the effects of 'selective' antagonists and a comparison has been made, for the alpha 2-subtype, with corresponding responses in the rat. In the rabbit the dose-response curve for phenylephrine was shifted to the right in parallel by prazosin (1 mg kg-1) and was unaffected by rauwolscine (1 mg kg-1). The dose-response curve for noradrenaline was shifted to the right by prazosin (1 mg kg-1) and was shifted to a smaller extent by rauwolscine (1 mg kg-1) or imiloxan (10 mg kg-1). After rauwolscine, prazosin produced a rightward shift larger than when given alone. After prazosin, rauwolscine produced a rightward shift larger than when given alone. The responses to pressor nerve stimulation at low frequencies (less than 1 Hz) could be reduced by prazosin, rauwolscine or imiloxan but those at a higher frequency could be reduced only by prazosin. These results indicate that the responses to noradrenaline or to nerve stimulation are mediated by both alpha 1- and alpha 2-adrenoceptors. Low doses or frequencies have a proportionately greater component which is alpha 2. Responses to noradrenaline after prazosin (1 mg kg-1), were sufficiently sensitive to rauwolscine to be considered as predominantly alpha 2. A comparison was therefore made of such responses in the rat and rabbit. They were produced by a lower dose per unit body weight in the rat whereas this was less marked for the alpha 2-adrenoceptor agonist guanabenz. In the rabbit they were more susceptible to blockade by rauwolscine but were less sensitive to Wy 26703 than in the rat. This demonstrates that the alpha 2-adrenoceptors mediating pressor responses in vivo, like those in other tissues in vitro, are different in rat and rabbit, with regard to antagonists.

L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney.

Rat kidneys were isolated and perfused with a modified Krebs-Henseleit buffer containing 4% albumin. Perfusate recirculated except during L-platelet activating factor (L-PAF), angiotensin II (ang II), and norepinephrine (NE) infusions. L-PAF caused a dose-dependent decrease in renovascular resistance (RVR): -6 +/- 3% at 10(-9)M, -12 +/- 6% at 10(-8)M, -18 +/- 3% at 10(-7) and -20 +/- 7% at 10(-6)M. L-PAF increased immunoreactive PGE (iPGE) and thromboxane (iTXB) release into the venous effluent from 2.4 +/- 0.2 to 3.9 +/- 0.4 ng/min (p less than 0.05) and from 2.1 +/- 0.4 to 3.5 +/- 0.5 ng/min (p less than 0.05), respectively. Vasodilation by L-PAF (10(-7) M) in the presence of indomethacin (INDO) (5 microM) was enhanced compared to the non-INDO response (RVR change: L-PAF = -18 +/- 3% vs. L-PAF = -26 +/- 3%; p less than 0.05). As a control for specificity, the was infused at 10(-9) M, 10(-8) M, and 10(-7) M. None of these concentrations changed renal vascular resistance. To study the vascular receptor responsible for L-PAF-induced vasodilation, dose-response curves to NE and ang II were established with and without L-PAF (10(-7) M). The NE dose-response curve was unchanged by L-PAF, whereas the ang II dose-response curve was shifted to the right by one order of magnitude. In kidneys pretreated with INDO (5 microM), the L-PAF-induced shift of the ang II dose-response relation was increased to 2-3 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of hepatic glycogen phosphorylase and glycogen synthase by calcium and diacylglycerol

Incubation of rat hepatocytes with angiotensin II (1 nM) produced a time-dependent accumulation of 1,2-diacylglycerol and inactivation of glycogen synthase with maximum effects at 10 min. The level of diacylglycerol then gradually declined and the activity of glycogen synthase I returned to control values at 30 min. In contrast, angiotensin II caused an increase in cytosolic Ca 2+ and an activation of glycogen phosphorylase which were rapid and transient, reaching maximum values in less than 2 min and then returning to control levels at 15 min. There were excellent correlations between the changes in glycogen synthase I and diacylglycerol levels and between the changes in phosphorylase α and cytosolic Ca 2+ in these time-course studies. However, there was no correlation between the changes in diacylglycerol and phosphorylase α or between the changes in cytosolic Ca 2+ and glycogen synthase I. Norepinephrine also caused a slow increase in diacylglycerol and inactivation of glycogen synthase, and a rapid increase in cytosolic free Ca 2+ and activation of glycogen phosphorylase. Addition of an α 1-adrenergic blocker (prazosin or phentolamine) caused rapid decreases in cytosolic free Ca 2+ and phosphorylase α, but only slowly reversed the inactivation of synthase and accumulation of diacylglycerol. The dose-response curves for norepinephrine and prazosin on glycogen synthase were well correlated with those on diacylglycerol. It is proposed that in liver cells, Ca 2+-mobilizing hormones regulate phosphorylase α through a Ca 2+-dependent mechanism and inactivate glycogen synthase through the generation of diacylglycerol, at least in part. The data provide additional support for the view that protein kinase C may be important in the regulation of glycogen synthase in liver.

A clinical approach for the identification of peripheral pre- and post-synaptic alpha-adrenergic receptors.

The present study examines the possibility that pre- and post-synaptic alpha-adrenergic receptors can be differentiated by a clinical pharmacological approach. We compared the ability of the alpha 1-selective antagonists, prazosin and urapidil, with the ability of the alpha 2-selective antagonist, yohimbine, to inhibit cardiovascular responses to the non-selective alpha-adrenergic agonist norepinephrine in 26 healthy volunteers. Urapidil (50 mg i.v.) and prazosin (5 mg orally) induced significant shifts to the right in the blood pressure dose-response curve of norepinephrine. Yohimbine (10 mg orally), on the other hand, increased norepinephrine sensitivity, as indicated by a significant shift to the left of the norepinephrine dose-response curve. In addition, urapidil and prazosin decreased norepinephrine potency on heart rate, whereas no effect on norepinephrine-induced heart rate elevation was observed with yohimbine. From the studies in which yohimbine was used it can be assumed that the post-synaptic response to norepinephrine is not counteracted by the drug-induced inhibition of sympathetic neurotransmitter release. Hence, our findings confirm the presence of pre- and post-synaptic alpha-adrenergic receptors in man.

Selective renal medullary damage and hypertension in the rat: The role of vasopressin

The induction of selective renal medullary damage by 2-bromoethylamine hydrobromide (BEA) results in polyuria and raised blood pressure. In view of the likely elevation of plasma vasopressin we have investigated the role of vasopressin (AVP) in the elevated blood pressure in this model. Plasma vasopressin levels in BEA pretreated rats were raised significantly (2 +/- 0.6 pg/ml vs 0.8 +/- 0.1 in normal rat, P less than 0.05) but not to pressor levels. In addition, pressor responsiveness was investigated in renal medullary damaged rats. There was a reduced response to vasopressin and noradrenaline but no alteration with angiotensin II. A specific V1, receptor AVP antagonist [d(CH2)5Tyr(Me)AVP] produced no fall in blood pressure but returned the noradrenaline dose-response curve to normal. This suggests an interaction between vasopressin and the sympathetic nervous system in this model. Thus there is no evidence that vasopressin contributes to the rise in blood pressure produced by chemical renal medullectomy and other mechanisms have to be sought.

Vasoconstriction induced by noradrenaline and angiotensin II is antagonized by eicosapentaenoic acid independent of formation of trienoic eicosanoids.

The isolated perfused rabbit ear was used to investigate the effect of eicosapentaenoic acid (EPA) on the vasoconstriction induced by noradrenaline (NA) and angiotensin II (A II). EPA (0.1, 1.0, 10.0 micrograms/ml) was shown to reduce the vasoconstriction (inhibition of flow) induced by NA in a dose-dependent manner. The dose-response curves of NA were shifted to the right. Emax of NA was reduced in particular at the highest concentration of EPA. The maximum effect of EPA developed slowly and reached a steady state after 150 min (0.1 microgram/ml EPA), 120 min (1.0 microgram/ml EPA), 100 min (3.0 microgram/ml EPA) and 60 min (10 micrograms/ml), respectively. In the presence of indomethacin (3 micrograms/ml), the vasoconstrictor effect of NA was not significantly influenced. The effect of EPA (3 micrograms/ml) was not reduced by indomethacin. In the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 micrograms/ml), the vasoconstrictor effect of NA was not significantly influenced. The effect of EPA (3 micrograms/ml) was not reduced by NDGA. Concomitant addition of indomethacin (3 micrograms/ml) and NDGA (10 micrograms/ml) also did not reduce the effect of EPA. EPA (3.0, 10.0 micrograms/ml) was shown to reduce also the vasoconstrictor effect of A II in the absence and the presence of the cyclooxygenase and lipoxygenase inhibitors. Determination by radioimmunoassay showed that the levels of thromboxane B2 (TXB2)-like immunoreactivity were below the detection limit in the perfusate of the ear. The levels of 6-keto-PGF1 alpha- and PGE2-like immunoreactivity in the perfusate were low. EPA reduced the concentration of 6-keto-PGF 1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

The facilitative actions of bay K 8644 on norepinephrine and KCL-induced contractures of rabbit aortic rings

The effect of the calcium channel agonist BAY K 8644 on the ability of KCl and norepinephrine to induce contractions of rabbit aortic rings has been examined in Krebs-Henseleit buffer containing either 4.0 or 6.8 mM potassium. BAY K 8644 (10 −8 to 10 −6 M) alone induced slowly developing aortic contractures which were 10 (at 4.0 mM potassium) or 20 (at 6.8 mM potassium) percent of the maximum obtainable with norepinephrine. These contractions were not observed in every experiment, but were more likely to occur at 6.8 mM (71% at 10 −6 M BAY K 8644) when compared to 4.0 mM (31% at 10 −6 M BAY K 8644) potassium buffer. BAY K 8644, in either potassium buffer, induced a statistically significant shift to the left in the norepinephrine dose-response curve. The norepinephrine dose-response curve was significantly curvilinear in the presence of 3 × 10 −8 M BAY K 8644 (6.8 mM potassium) and 10 −6 M BAY K 8644 (4.0 mM potassium). Similarly, BAY K 8644 induced sinistral shifts in the KCl dose-response curve with a curvilinear function observed at 3 × 10 −7 M BAY K 8644. These data show that BAY K 8644 is capable of inducing aortic contractures at potassium concentrations significantly lower than previously reported. Furthermore, BAY K 8644 facilitates opening of calcium channels by either potassium or norepinephrine. In contrast to others, our data indicates that BAY K 8644 can effect calcium channels activated by norepinephrine. Finally, our data suggest that the alpha and dihydropyridine receptors are capable of interacting and that occupation of one receptor can affect the action of a compound binding to the other receptor.

Presynaptic inhibitory effect of geographutoxin II, a new peptide toxin from Conus geographus venom, in the guinea-pig vas deferens

Geographutoxin II (GTX II), a new peptide toxin, isolated from Conus geographyus venom, caused a dose-dependent inhibition of the contractile response of the guinea-pig vas deferens to transmural stimulation at concentrations of 3 × 10 −8 to 10 −6 M. The dose-response curves for noradrenaline, acetylcholine and KC1 were not affected by GTX II (2 × 10 −7 to 10 −6 M). The release of noradrenaline induced by veratridine was strongly inhibited by GTX II. These results suggest that the GTX II-induced inhibition of the vas deferens may be a presynaptic effect causing a decrease of transmitter release.

Difference in Mode of Action of Alpha1-Adrenoceptor Antagonists on Some Vascular Smooth Muscles and Efficacy

Effect of YM-12617, a selective and potent alphai-adrenoceptor antagonist on dose-response curves of alpha1-adrenoceptor agonists, norepinephrine, phenylephrine and naphazoline, was tested in isolated rabbit vascular smooth muscles such as the femoral vein, portal vein and aorta. YM-12617 shifted the dose-response curves for norepinephrine and phenylephrine to the right and also declined the maximum response in the femoral vein, where norepinephrine and phenylephrine behaved as low efficacy agonists. Similar results were obtained on the curve of naphazoline in the portal vein, where the efficacy of naphazoline was low. Flowever, the efficacies of norepinephrine, phenylephrine and naphazoline were high in the aorta. The dose-response curves for three alphai-agonists were shifted by YM-12617 in a parallel manner in the aorta. The curves of norepinephrine and phenylephrine were also shifted by YM-12617 in the portal vein, where the efficacies of both the alpha1-agonists were high. The present results suggest that the mode of antagonism between the alpha1-agonist and alphai-antagonist is dependent on the efficacy of the alpha! -agonist which depends upon the receptor-density in the organ used.

Alpha 1-Adrenoceptor subtype mediating contraction of the smooth muscle in the lower urinary tract and prostate of rabbits.

The alpha-adrenoceptor subtype mediating contraction of the smooth muscle in the urinary bladder base (trigone), proximal urethra and prostate isolated from male rabbits was investigated by comparing the responsiveness to alpha-adrenoceptor agonists and antagonists under condition where beta-adrenoceptors and neuronal and extraneuronal uptakes were inhibited. Noradrenaline (non-selective), phenylephrine (alpha 1-selective) and clonidine (alpha 2-selective) caused a dose-dependent contraction in the trigone, urethra and prostate. Phenylephrine acted as a full agonist whereas clonidine was a partial agonist. YM-12617 and prazosin (alpha 1-selective), phentolamine (non-selective) and yohimbine (alpha 2-selective) produced dose-dependent shifts to the right of the dose-response curves for noradrenaline, phenylephrine and clonidine in the all three tissues. YM-12617 (pA2 = 9.77, 9.67 and 9.73 for trigone, urethra and prostate, respectively), prazosin (pA2 = 8.26, 8.20 and 8.08), phentolamine (pA2 = 7.67, 7.62 and 7.45) and yohimbine (pA2 = 6.30, 6.30 and 5.94) showed constant pA2 values irrespective of the agonists and tissues used, suggesting that only a single subclass of alpha-adrenoceptors is present. The actual pA2 values for these antagonists are comparable to those reported previously in tissues said to contain mainly alpha 1-adrenoceptors. Thus, we concluded that the postsynaptic alpha-adrenoceptors of the rabbit trigone, urethra and prostate mediating contraction belong to the alpha 1-subtype.

Increased forearm vascular reactivity in patients with hypertension after repair of coarctation.

To determine whether altered vascular reactivity could contribute to hypertension after repair of coarctation, the change in forearm and calf vascular resistances to small intra-arterial infusions of norepinephrine were measured in six patients who had undergone surgical correction of coarctation of the aorta but still had upper extremity hypertension and compared with similar measurements made in five normotensive patients with mild heart disease. Only the mean upper extremity pressure was significantly greater in the group that underwent repair of coarctation (102 +/- 11 vs 83 +/- 5 mm Hg, p less than .05, for mean arm pressures and 96 +/- 13 vs 83 +/- 7 mm Hg for mean leg pressures in patients who had coarctation vs normotensive patients, respectively). Forearm and calf blood flows were measured in the right arm and leg with a mercury-in-plastic strain-gauge plethysmograph. Forearm and calf vascular resistances were calculated by dividing mean arterial pressure of the appropriate extremity by the blood flow of that extremity. Norepinephrine was infused into the right brachial and femoral arteries of the patients at doses of 0.02, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7 microgram/min. Resting forearm and calf vascular resistances were similar in both groups of patients. The norepinephrine dose-response curves showed that control patients required more than three times the norepinephrine to produce the same percent increase in forearm vascular resistance (after 0.2 microgram/min forearm vascular resistance increased by 55% in the coarctation group, while the resistance in the control group increased by only 3%, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)