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Biomedical subjects

P Sever

Publications and source records attributed to P Sever.

53 records · Page 3Linked to original sources
PubMed1988

Action of dopamine on isolated human saphenous veins.

We have investigated the subtype of alpha-adrenoceptor responsible for the contractile effect of dopamine using isolated human saphenous vein. Lengths of saphenous vein were obtained surplus to coronary artery bypass graft operations and studied as intact rings using a conventional organ bath technique. Contractile responses to dopamine (10(-7)-10(-3) M) in the presence of propranolol, cocaine, and 17 beta oestradiol were competitively antagonised by the alpha 2-selective adrenoceptor antagonist yohimbine (10(-8)-10(-6) M) but unaffected by the alpha 1 selective adrenoceptor antagonist doxazosin (10(-8)-10(-6) M), whereas the response to norepinephrine (NE) (10(-8)-10(-3) M) was antagonised by doxazosin (10(-8)-10(-6) M), thus demonstrating the presence of alpha 1-adrenoceptors in this preparation. We conclude that the contractile effects of dopamine in isolated human saphenous vein are mediated predominantly by an action on alpha 2-adrenoceptors.

Aged↗
PubMed1987

Autoradiographic localisation of NPY receptors in rabbit kidney: comparison with rat, guinea-pig and human.

In vitro labelling of neuropeptide Y binding sites with 125I-NPY was performed in rabbit kidney sections. Autoradiographic and histochemical techniques localised these binding sites to the proximal convoluted tubules and the vascular smooth muscle. In comparison, 125I-NPY binding was absent from the rat, guinea pig and human kidney. Possible physiological roles for the putative NPY receptors in rabbit renal function are discussed.

Animals↗
PubMed1987

No evidence for a direct vasodilatory effect of celiprolol on human vasculature in vivo or in vitro.

Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arterial celiprolol (1-100 micrograms/min i.a.) on forearm blood flow (FBF). Forearm blood was measured by venous occlusion plethysmography. Possible vasorelaxant actions of celiprolol on human vascular smooth muscle were studied using segments of isolated human saphenous vein in vitro. The effect of celiprolol was investigated on resting tone or noradrenaline induced tone. Possible alpha 2-adrenoceptor antagonist effects of celiprolol were assessed using celiprolol as an antagonist of BHT933 induced constriction. Celiprolol was without significant effect on FBF and failed to relax isolated saphenous vein segments preconstricted with noradrenaline. The weak alpha 2-adrenoceptor antagonist action of celiprolol was demonstrable in human saphenous vein. This study does not provide evidence for a direct vasodilatory effect of celiprolol on human vasculature.

Adrenergic beta-Antagonists↗
PubMed1986

The action of a dopamine (DA1) receptor agonist, fenoldopam in human vasculature in vivo and in vitro.

This study was designed to investigate dopaminergic mechanisms in human vasculature using the selective vascular dopamine receptor agonist fenoldopam in vivo and in vitro. In vivo, forearm blood flow was measured plethysmographically and in vitro isolated rings of human blood vessels from a variety of sites were used for tissue bath studies. Intra-arterial fenoldopam markedly increased forearm blood flow, this effect was antagonised by (R) sulpiride, a vascular dopamine (DA1) antagonist, but not by metoclopramide, a neuronal (DA2) antagonist, or by guanethidine, an adrenergic neurone blocking agent. In vitro, fenoldopam relaxed preconstricted human renal, mesenteric and lumbar arteries, but not saphenous vein in a concentration dependent manner. (RS) sulpiride and SCH 23390 competitively antagonised this effect. These studies demonstrate the presence of a vasodilatory vascular dopamine receptor in man both in vivo and in vitro.

Adolescent↗
PubMed1985

Blood pressure patterns in relation to age, weight and urinary electrolytes in three Kenyan communities.

The blood pressure patterns of three Kenyan communities have been studied: 861 members of the Luo tribe in a rural community, 281 members of the Kamba tribe in a rural community and 310 "urban" Luo living in Nairobi. The slope of linear regression of blood pressure with age was significantly different in each population: rural Luo had the smallest rise with age and urban Luo had the largest rise with age, while the Kamba tribe were in between. The differences could not be accounted for by weight. Urinary electrolyte data showed rural Luo had the lowest sodium ratios (sodium/creatinine, sodium/potassium) and the highest potassium/creatinine ratio: urban Luo had the highest sodium and lowest potassium ratios and rural Kamba had values in between. The differences in blood pressures between the two groups of the same tribe in different environments (rural and urban Luo) were far greater than those between different genetic groups (Kamba and Luo) underlining the importance of environmental factor(s) in the determination of arterial pressure. Furthermore, these data support the theory that the dietary intake of sodium and potassium are the major influential environmental factors affecting blood pressure.

Adolescent↗
PubMed1985

Human vascular smooth muscle responses mediated by alpha 2 mechanisms in vivo and in vitro.

The effects of compounds with alpha 2-agonist and alpha 2-antagonist properties on human forearm blood flow and on isolated human arterial segments have been studied. The findings from these studies in vivo and in vitro did not provide evidence in support of the hypothesis that postsynaptic alpha 2-receptors mediate smooth muscle contraction in the tissues under investigation. The constriction of the forearm vascular bed in response to low intra-arterial doses of idazoxan (RX 781094), an alpha 2-antagonist, provides evidence for a physiological role for a presynaptic alpha 2 autoregulatory mechanism. The variability of the forearm vascular responses to higher doses of idazoxan highlights the pitfalls that may have misled previous authors in their interpretation of the results of similar studies. A U-shaped dose-response curve to compounds with mixed alpha 2- and alpha 1-antagonist properties may be constructed, which emphasizes the importance of the dose-dependent selectivity of these antagonists at alpha 2- and alpha 1-receptors. The effect of idazoxan on the responses of arterial segments in vitro to exogenous catecholamines was dependent on the integrity of the endothelium, and provides evidence that alpha 2-receptors may mediate release of the endothelium-derived relaxing factor.

Adrenergic alpha-Agonists↗
PubMed1982

Increased numbers of alpha receptors in sympathetic denervation supersensitivity in man.

Cardiovascular responses to intravenous administration of norepinephrine and the properties of alpha receptors on platelets were compared in normal human subjects and subjects with multiple system atrophy (MSA) and sympathetic degeneration. All the subjects with MSA had low plasma norepinephrine concentrations (in the supine position) (0.42 +/- 0.09 nM, normal 3.47 +/- 0.58 nM), which did not increase on tilt. The pressor sensitivity of subjects with MSA to norepinephrine infusion was increased 10- to 20-fold, demonstrating denervation supersensitivity to adrenergic agonists. Analysis of alpha receptors was by binding of [3H]dihydroergocryptine to platelets. Results are shown as mean +/- standard error of the mean. In the MSA subjects, the number of alpha receptors (1,712 +/- 699 fmol/10(8) platelets) was about sevenfold greater than in normal subjects (224 +/- 21 fmol/10(8) platelets), and the affinity, as measured by the equilibrium dissociation constant (Kd), was similar in both groups (MSA subjects, 9.6 +/- 4.3 nM; normal subjects, 4 +/- 0.5 nM). These observations suggest that an increase in alphaadrenergic receptor numbers may account for the denervation supersensitivity to infused norepinephrine in patients with sympathetic degeneration. All the subjects with MSA had low levels of the endogenous adrenergic transmitter norepinephrine: the simultaneous increase in alpha adrenergic receptors supports the theory of agonist regulation of receptor numbers.

Adult↗
PubMed1979

Baroreflex control of blood pressure and plasma noradrenaline during exercise in essential hypertension.

1. Twelve subjects (mean age 46.3 +/- 12.5 years) with mild to moderate hypertension were studied before, during and after bicycle ergometer exercise. 2. Baroreflex sensitivity was determined by the Oxford phenylephrine method; sensitivity at rest was inversely related to intra-arterial pressure and age. Age and resting arterial pressure were not related. 3. Exercise for 5 min at 50 W and 5 min at 75 W raised the mean arterial pressure from 116.4 +/- 18.0 to 150.0 +/- 25.4 mmHg, the heart rate from 73.2 to 126.7 beats/min and the plasma noradrenaline from 541 +/- 142.7 to 1309.8 +/- 543.5 pg/ml (P less than 0.001). 4. The increase in noradrenaline during exercise and the maximum mean pressure achieved were inversely related to resting baroreflex sensitivity (r = -0.68 and -0.77 respectively). Resting values of noradrenaline were not related to baroreflex sensitivity, age, or resting blood pressure. 5. It is possible that the rise in both plasma noradrenaline and arterial blood pressure produced by exercise is controlled by the baroreceptor reflexes; these are less effective in hypertensive subjects and thus the increases in noradrenaline and arterial pressure during exercise are greater in subjects with raised blood pressure.

Adult↗
PubMed1979

Defective cardiovascular reflexes and supersensitivity to sympathomimetic drugs in autonomic failure.

In 10 patients with chronic autonomic failure the clinical features and cardiovascular reflexes were correlated with the pressor responses to intravenous noradrenaline and tyramine. In all patients there was an exaggerated response to noradrenaline but a normal or only mildly exaggerated response to tyramine. Patients with lack of sinus arrhythmia and by implication baroreceptor reflex loss had greater responsiveness to pressor drugs than patients with preservation of this reflex. The responses to tyramine infusions imply that there must be sufficient noradrenaline released at defective sympathetic endings for a pressor response to occur. However, the lack of rise of plasma noradrenaline following tyramine, except in the patients with pure autonomic failure, clearly separates these responses from those of normal subjects. These results can be explained by the presence of lesions of both central and peripheral sympathetic pathways in patients with chronic autonomic failure and multiple system atrophy or Parkinsonism. The peripheral lesion, which is incomplete, may consist of replication of the receptors so causing supersensitivity with a duration of response that is little prolonged. The peripheral defect in the two patients with pure autonomic failure was found to be more complex and the prolonged response in one of these patients suggests the possibility of defective re-uptake or metabolism of noradrenaline. Clearly further study of the defects of sympathetic endings is required, including the use of other techniques such as catecholamine fluorescence. The extreme supersensitive responses underline the need for blood pressure monitoring during pressor drug studies prior to treatment, if the hazards of recumbent hypertension are to be avoided.

Adult↗
PubMed1979

The pressor actions of noradrenaline, angiotensin II and saralasin in chronic autonomic failure treated with fludrocortisone.

1 Treatment of postural hypotension due to chronic autonomic failure with fludrocortisone increased the pressor sensitivity to intravenous noradrenaline. Fludrocortisone increased the blood pressure in the standing but not the lying position. These effects of fludrocortisone may be the result of increased sensitivity of vascular receptors to noradrenaline. 2 The pressor action of angiotensin II, to which patients were supersensitive, may have involved the stimulation of alpha-adrenoceptors since it was partially antagonised by phentolamine. 3 Saralasin had a marked, paradoxical, pressor effect. This may have been mediated by vascular alpha-adrenoceptors because log dose-response curves of saralasin-induced increases in systolic pressure were shifted to the right in a parallel fashion after phentolamine. 4 Fludrocortisone treatment increased the pressor sensitivity to intravenous saralasin but not to angiotensin-II.

Aged↗
PubMed1978

Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure. Limitations and hazards.

The short-term effects of pressor amines were investigated in four patients with postural hypotension caused by autonomic failure. In supine patients p-tyramine alone or with a monoamine-oxidase inhibitor produced pronounced supine hypertension without abolishing the symptoms associated with a postural fall in blood-pressure. Phenylephrine or ephedrine maintained a normal blood-pressure on standing but caused supine hypertension. Thus the effects of p-tyramine with or without a monoamine-oxidase inhibitor were unpredictable and did not include relief of postural hypotension. Phenylephrine or ephedrine had some beneficial effect, but since all these drugs influence standing pressure only at the expense of pronounced supine hypertension, alternative therapy must be sought.

Aged↗
PubMed1977

Effects of clonidine on biochemical indices of sympathetic function and plasma renin activity in normotensive man.

1. A single oral dose of clonidine hydrochloride (300 microgram) lowered systolic blood pressure by 20+/-2 mmHg and diastolic blood pressure by 15+/-2 mmHg in seven healthy normotensive subjects. 2. Resting supine plasma noradrenaline concentration fell from 2-42+/-0-47 nmol/l before dosing to a minimum of 0-59+/-0-18 nmol/l at 6 h. The value subsequently rose and was not significantly different from that before the dose at 12 h. There was a significant reduction in urinary free catecholamine excretion in the first 12 h after dosing. 3. Resting supine plasma renin activity before dosing was 0-95+/-0-16 pmol of angiotensin I h-1 ml-1 of plasma and rose significantly after clonidine to 3-50+/-0-39 pmol of angiotensin I h-1 ml-1 of plasma at 6 h. By 12 h plasma renin activity had returned to control values. 4. When the same subjects were studied on a control, drug-free, day under the same conditions, there was no significant change in blood pressure or plasma noradrenaline. Although plasma renin activity rose during this control day, it was significantly lower than after clonidine. 5. In normotensive subjects single doses of clonidine lower blood pressure and are associated with a reduction of sympathetic nervous activity. Delayed elevation of plasma renin activity may be secondary to the fall in blood pressure. There is no evidence for an overshoot of sympathetic activity after a single dose of clonidine.

Adult↗