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Biomedical subjects

H Thurston

Publications and source records attributed to H Thurston.

At least 73 records · Page 4Linked to original sources
PubMed1986

Plasma noradrenaline in Goldblatt models of renovascular hypertension in the rat, before and after surgical reversal.

Plasma noradrenaline (NA), blood pressure (BP) and heart rate (HR) were measured simultaneously in conscious rats under basal conditions in the early phase (4-6 weeks) of one-kidney, one-clip hypertension (1K1C), in the early (4-6 weeks) and chronic (greater than 16 weeks) phases of the two-kidney, one-clip model (2K1C) and in age-matched loose clip control animals before and 2 days after unclipping. The elevated BP in all three hypertensive groups fell to normal after unclipping, whereas removal of the constricting clip in loose clip controls had no effect on BP. Plasma NA was elevated in 1K1C hypertension (P less than 0.05) and fell slightly but non-significantly on unclipping. However, in the early phase of 2K1C hypertension plasma NA was unaltered before and rose significantly (P less than 0.05) after unclipping. Plasma NA did not change with unclipping in the chronic phase of 2K1C hypertension and was not different from controls. Unclipping loose clip control animals produced no change in plasma NA. Changes in HR on unclipping followed a similar pattern to changes in plasma NA: changes in the two variables were significantly correlated in all three models (1K1C: r = 0.61, P less than 0.005; early 2K1C: r = 0.45, P less than 0.05; chronic 2K1C: r = 0.62, P less than 0.01). However, BP was only correlated with plasma NA in 1K1C hypertension (r = 0.49, P less than 0.02) and not in either phase of the 2K1C model. There was also a highly significant correlation between HR and plasma NA in 1K1C hypertension (r = 0.71, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Ion transport in hypertension: are changes in the cell membrane responsible?

Disturbances in several, distinct cell membrane ion transport processes have been demonstrated in essential hypertension but their variable relationship to blood pressure in different populations has made it difficult to achieve a unifying hypothesis. We suggest that altered composition of the lipid fraction of the cell membrane is the common underlying factor. This would produce many of the reported perturbations of cell membrane properties and function, not all of which relate directly to the development of hypertension, but which act as markers for the underlying abnormality. However, functions such as phosphoinositol turnover, calcium binding and Ca2+,Mg2+-ATPase dependent calcium efflux, which are influenced by the lipid composition of the membrane, provide a possible link between the membrane disturbance, intracellular calcium, vascular smooth muscle contraction and blood pressure. Alteration in the lipid content of the cell membrane not only provides an explanation for the variability in the ion transport abnormalities between populations but perhaps also for some of the variability in blood pressure within a single population. It also provides a potential means of influencing blood pressure by dietary intervention.

Animals↗
PubMed1986

Effects of changes in sodium balance on leucocyte sodium transport: qualitative differences in normotensive offspring of hypertensives and matched controls.

To investigate the effects of changes in sodium balance on blood pressure and leucocyte sodium transport, normotensive first-degree relatives of hypertensive patients and control subjects were randomized to receive low- and high-salt diets for 2 weeks, separated by a wash-out period of 2 weeks. High-salt intake failed to alter blood pressure, whereas the low-salt diet produced significant falls in standing pressures in both groups. In the control subjects leucocyte sodium efflux was not changed by either manoeuvre, but in the relatives low-salt diet stimulated ouabain-insensitive sodium efflux rate constant. There was a significant qualitative difference in the pattern of response of total efflux rate constant to the two dietary periods between the two groups of subjects. These data are not compatible with the release of a humoral sodium pump inhibitor in response to sodium-induced volume expansion, and lend support to a disturbance of membrane permeability to sodium in subjects genetically prone to hypertension.

Analysis of Variance↗
PubMed1986

Leukocyte ionized calcium and sodium content and blood pressure in humans.

The relationship between leukocyte ionized calcium concentration, sodium content, and blood pressure was studied in normotensive subjects with (n = 17) and without (n = 21) a family history of hypertension and in untreated patients with essential hypertension (n = 22). There was a highly significant correlation between intracellular ionized calcium and mean supine blood pressure (measured on the same occasion) in normal subjects with no family history of hypertension (r = +0.73, p less than 0.01). This relationship was lost in normal subjects with a family history of hypertension, and in hypertensive patients there was a nonsignificant negative correlation between intracellular ionized calcium and blood pressure (r = +0.08 and -0.31, respectively). Intracellular ionized calcium was similar in the normotensive groups (both, 126 +/- 7 nmol/L) and slightly but nonsignificantly elevated in hypertensive patients (143 +/- 10 nmol/L; p = 0.09). There was no correlation between intracellular ionized calcium and sodium content in any group (r less than 0.1). These results indicate that while leukocyte ionized calcium in normotensive subjects with no family history of hypertension may reflect smooth muscle contractility resulting in the positive correlation between leukocyte ionized calcium and blood pressure, this relationship is lost in hypertensive patients and subjects predisposed to hypertension. This may be due to an altered relationship between leukocyte and smooth muscle calcium handling in these subjects or to non-calcium-mediated influences on blood pressure.

Adult↗
PubMed1986

Vasodepressor mechanisms in experimental hypertension: studies using chemical medullectomy.

There is evidence that neither activation of the renin-angiotensin system nor changes in sodium balance can fully explain the maintenance of blood pressure in Goldblatt hypertension. Thus, in Goldblatt two-kidney, one clip hypertension in the rat sodium balance is negative and in hypertension of a few months' duration plasma renin initially elevated has returned to normal. When hypertension is reversed by removal of the constricting clip from the renal artery, blood pressure falls within a matter of hours even when hypertension has been present for many months, suggesting that the effect of structural changes in vascular resistance vessels has been overcome. In addition, blockade of the renin-angiotensin system during renal artery declipping does not influence the pattern of the blood pressure fall. We investigated the role of the renomedullary vasodepressor system by inducing medullary necrosis with 2-bromo-ethylamine hydrobromide. This causes a moderate blood pressure increase in normal rats, and partly inhibits the fall of blood pressure in Goldblatt two-kidney, one clip hypertension when the renal clip is removed. Chemical medullectomy is associated with a slightly negative sodium balance, plasma volume contraction, a reduction in plasma renin activity and urinary PGE2, and a minimal elevation in plasma vasopressin. Blood pressure elevation appears to be attributable to inhibition of a vasodepressor system based on the renal medulla. Chemical medullectomy offers a valuable tool for investigating the role of this medullary vasodepressor system.

Animals↗
PubMed1985

Treatment of essential hypertension: changes in blood pressure, echocardiography and electrocardiography on three therapeutic regimes.

Forty-three patients with essential hypertension were randomly allocated to one of the following treatment regimes; - atenolol, atenolol and hydralazine or methyl dopa. Blood pressure fell into the normal range at 3 months and was similar in all 3 groups. Blood pressure remained controlled over the period of study. M-mode echocardiography was assessed initially, at 3, 6 and 12 months. All groups showed a fall in the measured indices towards the normal range with a significant reduction in left ventricular wall thickness at 3 months in the methyl dopa group and left ventricular mass in the atenolol group alone of 6 months. In conclusion, no one treatment regime appeared to have sustained advantages over another and none of the groups showed any deterioration on echocardiographic criteria during the study.

Adult↗
PubMed1985

Fluid volumes and hemodynamics in hypertension produced by chemical renal medullectomy.

We have investigated the mechanisms by which chemical renal medullectomy with 2-bromoethylamine hydrobromide (200 mg/kg body wt) produces hypertension in rats. Groups of chemically medullectomized rats were compared with normal rats and rats that had been partially nephrectomized to produce an equivalent fall in glomerular filtration rate. Mean arterial pressure was elevated in the medullectomized (142 +/- 6 mmHg) compared with normal rats (124 +/- 3). In the medullectomized animals this was associated with significant tachycardia (483 +/- 15 vs. 450 +/- 6 beats/min) and an increase in cardiac output (61.1 +/- 5.0 vs. 49.9 +/- 2.2 ml X min-1 X 100 g body wt-1). Plasma volume was significantly reduced in medullectomized rats (2.16 +/- 0.15 vs 3.29 +/- 0.20 ml/100 g body wt), whereas exchangeable sodium was unchanged (39.9 +/- 0.5 vs. 39.7 +/- 0.5 meq/kg body wt). By contrast, both plasma volume and exchangeable sodium were increased in partially nephrectomized rats. These results are consistent with the hypothesis that chemical medullectomy produces hypertension by increased selective sympathetic efferent activity, raising cardiac output and postcapillary venular resistance. This may be the consequence of reducing the secretion of a renomedullary humoral substance that normally inhibits such activity.

Animals↗
PubMed1985

Reversal of renovascular hypertension: a comparison of changes in blood pressure, plasma renin, and sodium balance in two models in rats.

Blood pressure changes produced by removal of the renal artery clip in two forms of experimental renovascular hypertension in the rat (two-kidney one-clip and one-kidney one-clip hypertension) have been studied in relation to sodium balance and the renin angiotensin system. Continuous records of arterial blood pressure in conscious, freely moving animals with hypertension of less than 6 weeks' duration showed similar baseline values. After unclipping, blood pressure fell to normal levels within 12 hours of operation, and the pattern of the fall was identical in both models. Plasma renin concentration was elevated in two-kidney hypertension and fell to normal by 24 hours after operation, remaining unchanged 6 days later, whereas in one-kidney hypertension it was normal before and after unclipping. Sodium balance became positive in two-kidney hypertension within 24 hours of unclipping and remained so at 7 days, and was significantly different from that in unclipped loose-clip controls (+2.54 +/- 0.55 mmol vs. +0.46 +/- 0.55 mmol at 7 days, P less than 0.05). In one-kidney hypertension, sodium balance was negative during the first 24 hours after operation, and remained slightly negative at 7 days compared with loose-clip controls (-0.34 +/- 0.23 mmol). The similarity in the pattern of blood pressure fall in these two models of renovascular hypertension, despite qualitative differences in the response of sodium balance and the renin-angiotensin system, suggests that a common mechanism is activated by unclipping. This mechanism cannot be explained solely in terms of changes in sodium balance or activity of the renin-angiotensin system.

Animals↗
PubMed1984

Noradrenaline: a circulating inhibitor of sodium transport.

Leucocytes were isolated from venous blood of 11 normotensive volunteers with no family history of hypertension and the sodium efflux rate constants determined both alone and in the presence of increasing physiological concentrations of noradrenaline. There was a significant dose dependent reduction of total sodium efflux rate constant due to a reduction in ouabain sensitive sodium pump activity, glycoside insensitive efflux rate constants being unaffected. The magnitude of this effect was similar to the reduction in leucocyte sodium efflux rate constants observed in hypertensive patients (and their normotensive relatives). The noradrenaline induced depression of sodium pump activity was prevented by propranolol in a further seven experiments, suggesting that the effect was mediated by beta adrenoceptors. Catecholamines possibly functioning as circulating inhibitors of sodium transport may contribute to some of the disturbances in membrane electrolyte handling both in essential hypertension in man and in some experimental models of hypertension.

Biological Transport, Active↗
PubMed1984

Effects of treatment for hypertension on cerebral haemorrhage and infarction.

One hundred and sixty nine patients admitted to hospital for stroke over 30 months were examined to see whether treating hypertension had influenced the incidence of cerebral haemorrhage and infarction. Seventy eight (46%) of them had normal blood pressure, 47 (28%) previously diagnosed hypertension for which they were receiving treatment, and 44 (26%) previously undiagnosed and untreated hypertension. Haemorrhagic stroke was commoner among patients with untreated hypertension, whereas infarction was commoner in patients with treated hypertension. Infarction and haemorrhage were equally prevalent in patients with normal blood pressure. Effective treatment in this population seemed to have had a substantially different impact on vascular disease, giving rise to cerebral haemorrhage as opposed to infarction. This is consistent with evidence from other studies that treatment for hypertension has little or no effect on the progression of atheroma.

Aged↗
PubMed1984

Effect of unclipping on pressor responses in rats with renovascular hypertension.

Pressor responses to angiotensin II and noradrenaline have been examined in two models of renovascular hypertension (two-kidney one-clip and one-kidney one-clip) before and 24 h after removal of the renal artery clip to examine the possible role of pressor hyper-responsiveness in the maintenance of hypertension. Early and chronic hypertension was studied to assess the part played by progressive structural hypertrophy. Plasma renin concentration was elevated in early two-kidney hypertensive rats, whereas it was similar to that in age-matched normal rats in early one-kidney and chronic two-kidney hypertensive rats. Twenty-four hours after unclipping plasma renin concentration was the same in all groups. Unclipping restored blood pressure to normal levels by 24 h, whereas sham-operated animals remained hypertensive. Angiotensin II responses in both early and chronic two-kidney one-clip hypertensive rats were lower than in age-matched normal rats. In unclipped rats responses were similar to those in normals. One-kidney hypertensive rats had similar angiotensin II responses to normal rats and there was no change with unclipping. Blockade of endogenous angiotensin II production by converting enzyme inhibition resulted in similar angiotensin II responses in hypertensive and unclipped groups. In normal rats, angiotensin II responses were inversely related to plasma renin concentration (r = -0.47, P less than 0.001). Angiotensin II responses in hypertensive and unclipped rats were found to show a similar relationship to plasma renin concentration as normal rats. Noradrenaline responses in hypertensive rats were similar to those in age-matched normals and there was no significant change with unclipping.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1984

Hypertension produced by chemical renal medullectomy: evidence for a renomedullary vasodepressor function in the rat.

The rat renal papilla was selectively destroyed by 2-bromoethylamine hydrobromide; increasing doses produced a graded severity of histological damage, polyuria and a reduction in urinary prostaglandin E2 excretion. Destruction of at least half of the papilla caused significant hypertension, but plasma renin concentration and plasma creatinine did not change. After graded medullary damage Goldblatt two-kidney, one-clip hypertension was induced. Four weeks later the severity of hypertension was similar in medulla-damaged and medulla-intact groups. When Goldblatt two-kidney, one-clip hypertension was reversed by removal of the renal artery clip, the blood pressure fall was less when the inner renal papilla was ablated than when it was intact, although plasma renin concentration and sodium balance were similar. The final blood pressure was similar to that observed in normal rats treated with 2-bromoethylamine compared with their respective controls. These findings are consistent with the hypothesis that the inner renal medulla produces a vasodepressor that influences blood pressure in normal rats, and also lowers blood pressure when two-kidney, one-clip hypertension is reversed surgically.

Animals↗
PubMed1984

Cell membrane handling of sodium, sodium balance, and blood pressure.

A variety of abnormalities in cell membrane cation handling have been reported in hypertension. It is not known whether abnormal transport serves as a marker of an underlying disturbance in cell membrane function or whether one or more of the abnormal transport processes participate directly in the sequence of events that cause hypertension. One critical area is the response of membrane sodium transport to salt depletion and loading. To elucidate a possible relationship between changes in sodium balance, membrane cation transport, and blood pressure, we studied the effect of salt depletion and loading in two cells from two separate species--the rat thymocyte and the human white blood cell. In each, severe salt depletion significantly reduced ouabain-sensitive sodium efflux, while salt loading produced a non-significant increase. No significant changes in the sodium efflux rate constant were observed in thymocytes from Okamoto-Kyoto spontaneously hypertensive rats or from rats with Goldblatt one-kidney, one-clip or deoxycorticosterone-salt hypertension when they were compared with appropriate controls. However, both Okamoto-Kyoto hypertensive rats and Kyoto controls showed a highly significant fall in the sodium efflux rate constant with age. These findings indicate that the reduction in sodium pumping observed in hypertensive human patients is not attributable directly or indirectly to salt excess, since in the two species studied reduced sodium pumping was a physiological response to salt depletion. Further, altered membrane transport of sodium may reflect factors that affect cell composition (such as age) rather than participate directly in the pathogenesis of hypertension.

Animals↗