PubMed Health⌕ Search

Biomedical subjects

P S Sever

Publications and source records attributed to P S Sever.

At least 19 recordsLinked to original sources
PubMed1992

Direct vascular actions of hydrochlorothiazide and indapamide in isolated small vessels.

The mechanism by which thiazides lower peripheral resistance is unresolved. The aim of this study was to investigate the mechanisms of the acute vasodilator action of hydrochlorothiazide and the 'thiazide-like' diuretic indapamide on human, guinea pig and rat small arteries. Vessels were mounted on a myograph and the relaxation profile of both drugs and interactions with K+ channels and the vascular eicosanoid system were studied. Neither drug had any relaxant effect in rat mesenteric vessels and indapamide did not relax human arteries. Hydrochlorothiazide in both human and guinea pig vessels produced significantly more relaxation of noradrenaline than K(+)-constricted vessels (P less than 0.001). Relaxation to hydrochlorothiazide was reduced in the presence of charybdotoxin. Maximal-induced hydrochlorothiazide relaxation was reduced by 64% in human arteries (P less than 0.001) and by 91% in guinea pig vessels (P less than 0.001). Incubation with glibenclamide and indomethacin had no effect on the relaxant activity of hydrochlorothiazide and indapamide. Indapamide-induced relaxation was unaffected in the presence of charybdotoxin. These results show marked differences in the acute vasodilator action of hydrochlorothiazide and indapamide. There appears to be involvement of Ca(2+)-activated K+ channels in the acute vasorelaxant activity of hydrochlorothiazide.

Animals↗
PubMed1992

Mechanisms of action of cicletanine in human and guinea pig resistance arteries.

Human subcutaneous (s.c.) arteries and guinea pig mesenteric vessels (internal diameter 150-570 microns) were isolated and mounted on a microvascular myograph. Cicletanine-induced relaxation curves were constructed after preconstriction with either depolarising potassium (KPSS) or norepinephrine (NE) and in the presence and absence of indomethacin, glibenclamide, or tetraethylammonium chloride (TEA). Using only guinea pig vessels, cicletanine relaxation curves were constructed with and without charybdotoxin. In human vessels, there was no significant difference between cicletanine-induced relaxation in vessels preconstricted with either NE or KPSS, and neither ATP-sensitive or Ca(2+)-activated K channels were involved. However, with indomethacin added, in human vessels the maximal response to cicletanine (30 microM) was reduced by 51% (p less than 0.05). In guinea pig mesenteric arteries, cicletanine (30 microM) produced a 95% relaxation of the NE-constricted vessel and only 30% relaxation of the KPSS-constricted vessel (p less than 0.001). There was no evidence for any involvement of the ATP-sensitive K channel or the eicosanoid system. The relaxation to cicletanine (less than 3 microM) in with TEA added was greatly reduced (p less than 0.001) and with charybdotoxin added the concentration response curve to cicletanine was shifted approximately 3 log units to the right (p less than 0.001), suggesting an involvement of Ca(2+)-activated K channels. The acute vasodilator action of cicletanine is complex, with multiple mechanisms of action, and the relative importance of these varies in different species or at least in different vascular beds.

Animals↗
PubMed1992

Neurally evoked responses of human isolated resistance arteries are mediated by both alpha 1- and alpha 2-adrenoceptors.

1. Human subcutaneous resistance arteries (internal diameter 113-626 microns) were mounted in an isometric myograph. Electrical field stimulation was applied either continuously in the form of a frequency-response curve or intermittently at 16 Hz. The magnitude of the maximum contraction induced by continuous stimulation expressed as a percentage of the response to a supramaximal concentration of noradrenaline (10 microM) was highly variable but unrelated to vessel calibre. Contractile responses to both continuous and intermittent stimulation were abolished by 1 microM tetrodotoxin. 2. Prazosin (100 nM and 1 microM, alpha 1-adrenoceptor antagonist) inhibited responses to continuous stimulation over a range of frequencies (2-8 Hz). The response to continuous stimulation at 8 Hz was inhibited by 78 +/- 6% by 1 microM prazosin. Rauwolscine (100 nM, alpha 2-adrenoceptor antagonist) had a smaller effect on contractions induced by continuous stimulation. Rauwolscine inhibited the response at 8 Hz by 36 +/- 6%. Rauwolscine at a higher concentration (1 microM) caused further inhibition of the response to continuous stimulation. Prazosin and rauwolscine in combination almost completely inhibited the response to continuous stimulation at concentrations of 1 microM. 3. Prazosin and rauwolscine inhibited responses to intermittent stimulation in a concentration-dependent manner. The IC50 for this action of prazosin was 3.7 +/- 1.6 nM and the maximum inhibition induced by 100 nM prazosin was 78 +/- 6%. The IC50 of rauwolscine was 12.0 +/- 1.3 nM and 100 nM rauwolscine caused a 86 +/- 7% reduction in the response to intermittent stimulation.Prazosin and rauwolscine in combination (each at 100 nM) caused marked inhibition of the response to intermittent stimulation leaving only 7.0 +/- 2.6% of the response.4. These data suggest that neurally released noradrenaline evokes contractions of human resistance arteries by activation of both alpha 1,- and alpha 2-adrenoceptors postjunctionally.

Arteries↗
PubMed1992

Interaction between cicletanine and the eicosanoid system in human subcutaneous resistance arteries.

In human subcutaneous resistance arteries in-vitro, the relaxation produced by the novel furopyridine compound cicletanine (30 microMs) was inhibited by 51% (P less than 0.0001) in the presence of 20 microMs of the cyclo-oxygenase inhibitor indomethacin. Maximal cicletanine-induced relaxation was reduced by both the cyclo-oxygenase inhibitor mefenamic acid and the relatively specific blocker of prostacyclin synthetase, tranylcypromine by 55% (P less than 0.0005) and 43% (P less than 0.01), respectively. The potassium channel blocker, glibenclamide (100 microMs), did not affect the relaxation produced by cicletanine but did inhibit the relaxation produced by the potassium channel blocker cromakalim (P less than 0.0001). Cromakalim-induced relaxation was inhibited in the presence of indomethacin; relaxation induced by cromakalim (30 microMs) was reduced by 22% (P less than 0.02). The relaxation produced by the hypotensive agonists sodium nitroprusside, hydrochlorothiazide, bumetanide and nicardipine was unaffected by incubation with indomethacin. The results suggest that the vascular eicosanoid system, specifically prostacyclin, may be involved in the mechanism of the acute vasodilator action of cicletanine. Although at high doses, cicletanine is a diuretic, in this model it did not act like either a thiazide or a loop diuretic. The acute vasodilator action of the thiazide diuretic, hydrochlorothiazide was a novel finding of this study. Cromakalim showed a reduced response in the presence of indomethacin suggesting an involvement of the eicosanoid system in its mechanism of action.

Antihypertensive Agents↗
PubMed1992

Acute changes in haematological parameters on cessation of smoking.

Cigarette smoking is known to affect many haematological parameters but little is known of their rate of return to normal on withdrawal of cigarettes. Two groups of chronic smokers were studied whilst smoking and in the 2 weeks after cessation. A rapid return towards normal was found in the elevated haemoglobin concentration, packed cell volume, red cell count, white cell count, neutrophil count, lymphocyte count and platelet count, indicating that at least some of the abnormalities in these parameters are an acute, reversible effect of cigarette smoking rather than being a response to tissue damage.

Adult↗
PubMed1992

Conn's syndrome can cause malignant hypertension.

We present a case in which a patient, having already sustained an episode of malignant hypertension, was subsequently found to have an underlying Conn's adenoma. Ablation of the adenoma improved control of her hypertension. When a second adenoma developed in her remaining adrenal gland, control of her hypertension deteriorated.

Adenoma↗
PubMed1991

The effects of blood pressure reduction on abnormal left ventricular diastolic function in hypertensive patients.

To investigate whether reduction in blood pressure has a beneficial effect on left ventricular diastolic function, we investigated 20 hypertensive patients with evidence of diastolic dysfunction at baseline and at 3 and 6 months after initiation of captopril therapy. Two-dimensional echocardiography was used to determine left ventricular mass index and Doppler ultrasound to assess diastolic function. Fifteen of the 20 patients had a significant reduction in blood pressure at 3 and 6 months and left ventricular mass index remained unchanged during the study period. Despite reduction in blood pressure, no difference in isovolumic relaxation time, early and atrial filling velocities or their ratio was observed. Our results suggest that a direct relationship between blood pressure and left ventricular diastolic function does not exist and that other factors such as alterations in muscle or collagen composition of the left ventricle may be more important in determining abnormal diastolic function in hypertension.

Adult↗
PubMed1991

Haemorheological changes in the very short term after abstention from tobacco by cigarette smokers.

A study was made of the haemorheological changes that took place in the days immediately following tobacco withdrawal from cigarette smokers. In both males and females substantial and persistent reductions in blood viscosity occurred within 2 d, the fall at high shear rate corresponding to about 8% while at low shear rate it was approximately twice as much. These changes were due partly to a fall in packed cell volume (PCV), but also to reductions in total plasma protein and fibrinogen concentrations which led to reductions in plasma viscosity and rouleaux formation. These plasma protein-related changes were less pronounced in the female group. The results indicate that, even in the very short-term, abstention from cigarettes leads to substantial improvements in the haemorheological profile of heavy smokers.

Adult↗
PubMed1991

The effects of adenosine triphosphate (ATP) and related purines on human isolated subcutaneous and omental resistance arteries.

1. Human resistance arteries were obtained from specimens of omentum and subcutaneous fat removed at surgery. They were studied in vitro by use of a myograph technique to determine the effects of purines on the arteries. 2. In preparations where tone had been raised with noradrenaline, low concentrations (1 nM-1 microM) of adenosine triphosphate (ATP) and 2-methylthioATP, but not alpha,beta-methyleneATP, produced concentration-dependent relaxation. There was a lack of relationship between the relaxation response to acetylcholine and that to ATP. 3. In preparations under basal tone, high concentrations (1 microM-1 mM) of ATP, 2-methylthioATP and alpha,beta-methyleneATP produced concentration-dependent contractions. 4. The rank order of potency of the purine nucleotide analogues for the relaxation response was 2-methylthioATP > ATP > alpha,beta-methyleneATP and for the contractile response it was alpha,beta-methyleneATP > ATP = 2-methylthioATP. 5. Adenosine produced concentration-dependent relaxation in preparations under raised tone and was less potent than ATP but did not produce contraction in preparations at basal tone. Relaxation responses to adenosine, but not to ATP, were antagonized by 8-phenyltheophylline. 6. These results indicate the presence of vasodilator P2y- and P1-purinoceptors and vasoconstrictor P2x-purinoceptors on human resistance arteries isolated from omental and subcutaneous sites.

Adenosine Triphosphate↗
PubMed1991

Determinants of left ventricular filling in hypertension.

The relationship of left ventricular (LV) filling to the clinical and echocardiographic characteristics of 51 patients with untreated hypertension (borderline hypertension n = 17, essential hypertension n = 34) was investigated using two-dimensional echocardiography and Doppler ultrasound. Twenty-five patients had evidence of abnormal LV filling. Linear regression analysis revealed weak but significant correlations of LV filling with age (r = -0.53; P less than 0.0001), systolic blood pressure (r = -0.38; P less than 0.006), LV septal wall thickness (r = -0.44; P less than 0.0001) and LV mass index (r = -0.33; P less than 0.02). There was no association between LV filling and sex, race, heart rate or LV posterior wall thickness or cavity dimension. After stepwise regression analysis, age was found to be the only independent variable associated with LV filling, indicating that the other variables were dependent on age. This study suggests that a) abnormal LV filling is a frequent observation in hypertension b) LV filling is more dependent on age than blood pressure or LV size and c) other pathophysiological factors, so far undetermined, must contribute to the development of these abnormalities.

Adult↗
PubMed1990

Measurement of intracellular magnesium in a vascular smooth muscle cell line using a fluorescent probe.

Until recently, direct measurement of intracellular free magnesium has been complex and difficult. However, fluorescent probes are now available, based on the same principle as well-established probes for free calcium. Using one such probe, mag-fura-2, we have estimated basal intracellular magnesium concentrations in the A7r5 rat vascular smooth muscle cell line. This level was unaffected by numerous pharmacological manipulations, including agonist stimulation and depolarisation. The possible implications of these findings are discussed.

Animals↗
PubMed1990

Regression of hypertensive left ventricular hypertrophy and left ventricular diastolic function.

The effect of antihypertensive therapy on regression of left ventricular hypertrophy and left ventricular diastolic function was investigated in 25 hypertensive patients for up to 18 months after initiation of treatment. Left ventricular mass index was calculated by two-dimensional echocardiography and left ventricular diastolic function assessed by transmitral pulsed doppler ultrasound. Significant reduction in left ventricular mass index was observed after 9 months of treatment. Only 13 patients had a reduction in mass greater than the intraobserver variability of the technique. There was no change in doppler indices of left ventricular diastolic function. In 7 patients who were studied for a further 9 months after regression had occurred there was still no appreciable difference in left ventricular diastolic function. These findings indicate that there is no direct relation between left ventricular mass and abnormal left ventricular diastolic function.

Adult↗
PubMed1990

The Kenyan Luo migration study: observations on the initiation of a rise in blood pressure.

OBJECTIVE: To demonstrate the magnitude, timing, and cause of changes in blood pressure that occur in migrants from a low blood pressure population on moving to an urban area. DESIGN: A controlled longitudinal observational study of migrants as soon after migration as possible and follow up at three, six, 12, 18, and 24 months after migration. A cohort of controls living in a rural area who were matched for age, sex, and locality were also observed at the same periods. SETTING: 35 Villages on the northern shores of Lake Victoria in western Kenya and Nairobi. PARTICIPANTS: 325 Members of the Luo tribe aged 15 to 34 years who had migrated to Nairobi and 267 controls living in villages. The numbers of both groups reduced during follow up such that only 63 migrants and 143 controls were followed up for two years. MAIN OUTCOME MEASURES: A medical questionnaire and three 24 hour diet histories were completed by migrants and controls. Height, weight, pulse, and blood pressure were measured. Three 12 hour overnight urine samples were collected from all participants and analysed for sodium, potassium, and creatinine concentrations. RESULTS: The mean systolic blood pressure of migrants was significantly higher than that of controls throughout the study, and the distribution of blood pressure was shifted to the right compared with controls. The mean diastolic blood pressure of the two groups diverged over time. Blood pressure differences were not due to selective migration. The migrants' mean urinary sodium:potassium ratio was higher than that of controls (p less than 0.001) throughout, and weight and pulse rate were also higher among migrants, although differences diminished with time. CONCLUSIONS: Urinary sodium:potassium ratio, pulse rate, and weight are important predictors of increased blood pressure among migrants from a low blood pressure community and may also be implicated in the initiation of essential hypertension.

Adolescent↗
PubMed1990

Phaeochromocytoma--investigation and management of 10 cases.

Since 1960 we have diagnosed phaeochromocytoma (paraganglioma) in 10 children. The cases include a 15 year old girl who over a three year period presented with multiple paragangliomata and an associated malignant carotid body tumour. All children were hypertensive, eight of 10 presenting with severe headaches. Diagnosis was based on finding a raised urinary vanillylmandelic acid excretion and plasma noradrenaline concentration. In addition six of eight children were hypercalcaemic with raised plasma calcitonin concentrations; plasma parathyroid hormone concentrations were high in two of seven and four out of eight children had raised plasma renin activities on presentation. No child, however, was found to have a multiple endocrine neoplasia syndrome. Despite the introduction of newer techniques for the detection of catecholamine producing tumours we found that selective arteriography and venous catecholamine sampling were superior for tumour localisation compared with ultrasound scanning, computed tomography, and metaiodo-benzyl-guanidine (MIBG) scanning.

Adolescent↗