Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension

Esler, Murray; Jackman, Graham P.; Leonard, P; Bobik, Alex; Skews, Helen; Jennings, Garry; Kelleher, Dianne; Korner, Paul I.

doi:10.1042/cs059311s

Cited by 28 publications

(14 citation statements)

References 7 publications

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“…Additional factors influencing the plasma NE levels include variation in distribution and rate of metabolism, which VOL 5, No 1, JANUARY-FEBRUARY 1983 is seen in normal subjects, 32 hypertensive patients, autonomic insufficiency, and following drug interventions. 33 It may be for this reason that there is dispute as to the interrelationship between baseline plasma NE levels and the presence and extent of hypertension. 22 ' 3K 34~36 However, plasma NE levels are considered to be representative of sympathetic nerve activity.…”

Section: Discussionmentioning

confidence: 99%

Baroreflex sensitivity modulates vasodepressor response to nitroprusside.

Shepherd¹,

Lin

McNay

et al. 1983

Hypertension

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SUMMARY Baroreflex activity is a determinant of the homeostatic response to alteration in blood pressure. We examined the factors that determine the magnitude of the vasodepressor response to sequential incremental intravenous infusions of sodium nitroprusside (NP), 0.05 to 6.4 yug/kg/min, in eight male patients with essential hypertension. Each infusion level was of 10 minutes' duration. Change from control values of mean arterial pressure (AMAP), heart rate (AHR) and plasma norepinephrine (ANE) were obtained at the end of each infusion level. Significant correlations were found between AMAP vs log dose NP, AHR vs AMAP and ANE vs AMAP for each patient (p < 0.05). However, the slopes of these relationships varied widely between subjects and were significantly correlated with the control blood pressure of each patient. In addition, the sympathetic responsiveness, as measured by ANE vs AMAP, was inversely correlated with the degree of vasodepressor response seen. Thus, the magnitude of the vasodepressor response was determined by two major factors: 1) the predrug blood pressure, possibly reflecting altered vascular geometry with hypertension; 2) the degree of sympathetic response, which probably acts by mediating the degree of reflex alpha-adrenergic-mediated arteriolar vasoconstriction. (Hypertension 5: 79-85, 1983) KEY WORDS * plasma norepinephrine • hypertension • heart rate • humans T HE level of baroreceptor activity, acting by way of the sympathetic nervous system, is a major determinant of the homeostatic response to perturbation of blood pressure. Changes in sensitivity of the baroreflex arc occur in hypertension, 1 " 5 sleep, 6 and with aging. Baroreflex sensitivity (BRS) is usually expressed in terms of the change in heart rate (HR), or R-R interval, for each unit of change in blood pressure.' 2 7~9 However, there are practical and theoretical limitations to this approach. First, in subjects receiving beta-adrenoceptor antagonists, the relationship between HR response and the level of sympathetic activity may change. Second, HR is controlled by a balance between the level of activity of the vagal and the sympa-

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Section: Discussionmentioning

confidence: 99%

Baroreflex sensitivity modulates vasodepressor response to nitroprusside.

Shepherd¹,

Lin

McNay

et al. 1983

Hypertension

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“…A few other groups of investigators have compared plasma NE disappearance in hypertensive and normotensive groups (22,23,27,28) after an infusion to steady state, with discrepant results. Esler and coworkers found that the first half-life of NE disappearance is prolonged in a minority of patients with essential hypertension (22), which they attributed to decreased U1 (29).…”

Section: Discussionmentioning

confidence: 99%

“…In an attempt to measure separately the contributions of these factors in determining plasma NE in patients with essential hypertension, Esler and associates (22,23) early, rapid half-life (t1/20) of -2 min and later with a slower half-life (t1/2b) of >30 min; that desipramine prolonged t1/2a; and that a subgroup of hypertensive patients showed prolongation of t1/2a. They concluded that in some patients with essential hypertension, faulty U, could account for elevated circulating levels of NE and the patients' high blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

Goldstein¹,

Horwitz²,

Keiser³

et al. 1983

J. Clin. Invest.

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A B S T R A C T We infused tracer-labeled 1-[3H]-norepinephrine, d-['4C]norepinephrine, and d,l-[3H]isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of 1-or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The dli ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.

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“…Indeed, in studies in which the neuromuscular junction has been assessed in essential hypertension by measurements of the rate at which [ 3 H]norepinephrine is removed from the plasma, there is evidence of an impairment in the neuronal uptake of norepinephrine. 35 " 37 The reason for this lack of effect of cocaine is currently difficult to explain. In other experiments in our laboratory we have found that cocaine in cannulated and pressurized vessels has no effect on the concentration-response relation of norepinephrine in rat mesenteric vessels from both spontaneously hypertensive and normotensive Wistar-Kyoto rats, whereas on the wire myograph the concentration-response curves are shifted to the left (unpublished data).…”

mentioning

confidence: 99%

In vitro perfusion studies of human resistance artery function in essential hypertension.

Falloon

Heagerty

1994

Hypertension

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To simulate in vivo conditions as closely as possible to in vitro conditions, we examined the morphological and functional characteristics of isolated human subcutaneous small arteries from 17 essential hypertensive patients and 14 normotensive control subjects using a perfusion myograph. Vessel segments were cannulated and exposed to conditions of constant flow and pressure. The ratio of media thickness to lumen diameter in arteries from hypertensive patients increased significantly. With the endothelium intact, sensitivity to extraluminally applied norepinephrine was not different, and this was not affected by inhibition of neuronal amine uptake with cocaine. After removal of the endothelium, sensitivity to norepinephrine was augmented in normotensive vessels to a greater extent than in hypertensive vessels. Endo-

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Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension

Cited by 28 publications

References 7 publications

Baroreflex sensitivity modulates vasodepressor response to nitroprusside.

Baroreflex sensitivity modulates vasodepressor response to nitroprusside.

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

In vitro perfusion studies of human resistance artery function in essential hypertension.

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