Biomedical subjects

P Korner

Publications and source records attributed to P Korner.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Assessment of neuronal uptake of noradrenaline in humans: defective uptake in some patients with essential hypertension.

1. Disappearance of tritiated noradrenaline from plasma, after infusion to steady-state, was studied to assess neuronal uptake of noradrenaline inessential hypertension. 2. Plasma tritiated noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed both in normal subjects after desipramine, and in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In nine of thirty-eight hypertensive patients the t1/12 similarly was prolonged. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, was increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenergic recepotors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.

Adult↗

PubMedDate not supplied

Differing noradrenaline kinetics in essential hypertension and depressive illness, two diseases in which the plasma concentration of noradrenaline is sometimes elevated.

1. The rate of spill-over of noradrenaline to plasma, and neuronal noradrenaline uptake, which influences spill-over, were studied in patients with essential hypertension and depressive illness. 2. Noradrenaline spill-over was increased in seven of thirty-four patients with essential hypertension and five of eleven patients with primary depressive illness, compared with values in seventeen normal subjects (range 1.0-3.63 nmol/min per m2). 3. Faulty neuronal reuptake of noradrenaline seemed to be the cause of higher noradrenaline spill-over in patients with essential hypertension. Increased sympathetic nerve firing rates apparently were responsible in the primary depressives, despite their normal blood pressure. 4. These puzzling findings suggest that hypertension occurs when neurotransmitter excess is due to defective noradrenaline reuptake (in essential hypertension), but not chronically increased nerve firing (in depressive illness).

Adult↗

PubMedDate not supplied

Norepinephrine kinetics in essential hypertension. Defective neuronal uptake of norepinephrine in some patients.

To assess sympathetic nervous system function in essential hypertension, we measured the rates of release to and removal from plasma of the sympathetic neurotransmitter, norepinephrine. In normal subjects, disappearance of tritiated l-norepinephrine from plasma, after infusion to steady state, was biexponential, with t1 1/2 = 2.0 +/- 0.4 minutes (mean +/- standard deviation) and t2 1/2 = 33 +/- 15 minutes. The rapid component of removal seemed to represent neuronal uptake of norepinephrine: the t1 1/2 was lengthened by the selective inhibitor of neuronal norepinephrine uptake, desipramine; it was not changed by the extraneuronal uptake blocker, cortisol; and it was prolonged in patients with peripheral sympathetic nerve dysfunction (idiopathic autonomic insufficiency). In eight of 37 hypertensive patients, the t1 1/2 was greater than 2.8 minutes (range, 3.3-6.0 min), longer than in any normal subject; this appears to be presumptive evidence of the existence of defective neuronal norepinephrine uptake. In these patients the rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 +/- 0.39 micrograms/m2/min (4.3 +/- 2.3 nmoles/m2/min), higher than in normal subjects, 0.36 +/- 0.14 micrograms/m2/min (2.1 +/- 0.8 nmoles/m2/min) (p less than 0.01). A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local norepinephrine concentration, may be important in the pathogenesis of blood pressure elevation in some patients with essential hypertension.

Adolescent↗

PubMedDate not supplied

Contribution of central and peripheral mechanisms to the antihypertensive effects of alpha-methyldopa in the rabbit.

We compared the effects of one intracisternal (0.6 mg/kg i.c.) and two intravenous (25 and 50 mg/kg i.v.) doses of alpha-methyldopa (alpha-MD) on blood pressure, heart rate, and plasma catecholamines in rabbits before and 2-3 weeks after intracisternal administration of 6-hydroxydopamine (6-OHDA). Intracisternally administered alpha-MD lowered heart rate, blood pressure, and plasma noradrenaline levels. Peak effects on heart rate and blood pressure were observed 2-3 h after administration. Three hours after intracisternally administered alpha-MD, plasma noradrenaline levels were reduced by 58%. Two to three weeks after 6-OHDA administration, the central mechanism responsible for the falls in heart rate, blood pressure, and plasma noradrenaline levels was abolished. The effects of intravenously administered alpha-MD (50 mg/kg) on heart rate, blood pressure, and plasma noradrenaline levels were attenuated but not completely abolished by destruction of central catecholaminergic neurons with 6-OHDA. These residual effects of alpha-MD most probably represent the peripheral effects of alpha-methylnoradrenaline at sympathetic terminals. The relative magnitudes of central to peripheral effects of alpha-MD on heart rate and blood pressure are dose dependent. After the lower intravenous dose (25 mg/kg), which achieves plasma alpha-MD concentrations similar to those found in humans, central mechanisms predominant. At higher doses, central and peripheral mechanisms contribute equally to these effects.

Animals↗