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Biomedical subjects

J M Ledingham

Publications and source records attributed to J M Ledingham.

69 records · Page 4Linked to original sources
PubMed1970

Haemodynamic and other studies in the renoprival hypertensive rat.

1. The optimal conditions for the development of hypertension after total nephrectomy were defined in the rat. Under these conditions, haemodynamic changes were then studied before and for 3 days after total nephrectomy in the unanaesthetized animal and compared with mock-nephrectomized controls.2. Changes in cardiac output were followed with an electromagnetic flowmeter chronically implanted on the ascending aorta, and mean arterial pressure with an indwelling aortic cannula.3. Haematocrit fell in animals developing hypertension, due to plasma volume expansion. Restriction of administered saline did not reduce the fall in haematocrit without also preventing development of the hypertension.4. Cardiac output and stroke volume increased significantly on the second and third days after nephrectomy. Peripheral resistance remained unchanged and pulse rate tended to fall.5. The increase in cardiac output appeared to be more than could be accounted for by anaemia alone, and it is suggested that plasma volume expansion was partly responsible.6. In another group of rats developing renoprival hypertension a correlation was found between changes in plasma volume and arterial pressure over the three days.7. Renoprival hypertension was accompanied by a slight but significant reduction in oxygen consumption in comparison with the controls.8. No relationship was found between the changes in blood pressure, and plasma sodium and potassium levels.9. It is concluded that the observed rise in cardiac output associated with renoprival hypertension as induced in this study was not attributable to anaemia nor to a rise in metabolic rate. The implications of this situation are discussed in relation to a theory of the pathogenesis of hypertension and the findings of other workers.

Animals↗
PubMedDate not supplied

Remodelling of resistance arteries in genetically hypertensive rats by treatment with valsartan, an angiotensin II receptor antagonist.

1. In the present study, New Zealand genetically hypertensive (GH) rats were treated with valsartan, a specific angiotensin II (AT1) receptor antagonist, to measure the effects on blood pressure (BP), cardiac hypertrophy and the structure of resistance arteries. Normotensive (N) rats were used as controls. 2. Valsartan (val) was given to GH rats at three different doses (10, 3 or 0.3 mg/kg per day, via osmotic mini-pumps implanted i.p.) from age 4-10 weeks. Untreated GH (mini-pump + vehicle) and N rats (mini-pump + vehicle) were used as controls. BP was measured weekly and at the end of the experiment, left ventricular (LV) mass was recorded and the structure of mesenteric resistance arteries (MRA) was determined using stereological methods. 3. BP fell in a dose-dependent fashion, being reduced to normotensive levels by 10 mg/kg; LV mass was significantly reduced (P < 0.0001) to below normotensive values in the GH group given 10 mg/kg val and significantly reduced (P < 0.001), although not normalized, in the other two treatment groups. 4. In MRA, the media/lumen (M/L) ratio was reduced by val according to dose level, to below normotensive values in GHval10, and to levels not different from normotensive values in the GHval3 and GHval0.3 groups. 5. The hypertrophy of smooth muscle cells in GH rats was reduced with val treatment at all doses. 6. Reversal of cardiac and vascular hypertrophy occurred even when BP was not reduced to normotensive levels, indicating an effect on vessel growth but without any retardation of body growth. 7. These results suggest that the vascular structural changes seen after val and angiotensin converting enzyme inhibitor treatment are probably due to the blocking of angiotensin rather than any bradykinin effect.

Angiotensin II↗
PubMedDate not supplied

Prevention of increases in blood pressure and left ventricular mass and remodeling of resistance arteries in young New Zealand genetically hypertensive rats: the effects of chronic treatment with valsartan, enalapril and felodipine.

The relative efficacy of three antihypertensive drugs in the prevention of further elevation of blood pressure (BP) and cardiovascular structural remodeling in 4-week-old genetically hypertensive (GH) rats was studied by means of two complementary methods, stereology and myography. Four to 10-week-old GH rats were treated with valsartan (10 mg/kg/day), enalapril (10 mg/kg/day) or felodipine (30 mg/kg/day). Untreated GH and normotensive control rats of Wistar origin served as controls. Tail-cuff systolic SBP was measured weekly and left ventricular (LV) mass determined at the end of the experiment. Mesenteric resistance arteries (MRA) were either fixed by perfusion, embedded in Technovit and sections stained for stereological analysis, or mounted on a wire myograph for structural and functional measurements. BP and LV mass were significantly reduced by all drugs; decreases in BP and LV mass were smaller after felodipine treatment. Valsartan and enalapril caused a decrease in BP to normotensive control values. Felodipine kept BP at the 4-week level and prevented further rise with age. Valsartan caused hypotrophic outward remodeling of MRA, enalapril eutrophic outward remodeling and felodipine hypotrophic remodeling. Myograph measurements showed remodeling of the same order. While all drugs lowered the media/lumen ratio in GH to normal, the outward remodeling after valsartan and enalapril indicates that valsartan and enalapril might be more effective in reversing the inward remodeling of resistance arteries found in essential hypertension.

Animals↗
PubMedDate not supplied

Prolonged isometric exercise. Part 1: Effect on circulation and on renal excretion of sodium and potassium in mild essential hypertension.

The effect of stress, in the form of prolonged isometric exercise, on the circulation and on the renal excretion of sodium and potassium was studied in 18 patients with mild essential hypertension. Thirteen men and five women, aged 20 to 50 years with basal diastolic blood pressure (BP) between 90 and 110 mm Hg were matched by age, sex, and race with 18 controls who had basal diastolic BPs less than 85 mm Hg. After the subjects rested for 90 minutes, basal measurements of pulse rate, BP, and rates of sodium and potassium excretion were made. The subjects then underwent a 1-hour period of isometric exercise involving all four limbs in rotation, followed by 5 hours of rest during which the measurements were repeated at half-hourly intervals for the first 2 hours and at hourly intervals for the last 3 hours. On another day, the subjects were again studied after 1 hour of resting instead of exercise. Responses of each subject were then expressed as ratios of changes from the basal values observed on the exercise and rest days. Changes in systolic and diastolic BP and hart rate were not significantly different in the hypertensive and control groups. In hypertensive subjects, the rate of sodium and potassium excretion was decreased after isometric exercise compared with the rest day, whereas in normal subjects this response was reversed. For the first 3 hours after exercise, the cation excretion rate of the hypertensive group was significantly less than that of the control group. These results indicate that isometric exercise in mild hypertension induces prolonged renal retention of both sodium and potassium.

Adult↗
PubMedDate not supplied

Prolonged isometric exercise. Part 2: Effect on circulation and on renal excretion of sodium and potassium in young males genetically predisposed to hypertension.

The effect of stress, in the form of prolonged isometric exercise, on the circulation and on the renal excretion of sodium and potassium was studied in 16 male medical students whose parental blood pressure (BP) was less than 140/85 mm Hg, and in 17 male students with one or two parents who had BPs greater than 150/95 mm Hg. After the subjects rested initially for 90 minutes, basal measurements were made of heart rate, BP, and the rates of sodium and potassium excretion. The subjects then underwent a 1-hour period of intermittent isometric exercise involving all four limbs in rotation, during which BP and heart rate were measured. A 5-hour period of rest followed, during which BP, heart rate, and the rate of electrolyte excretion were measured at half-hourly intervals for the first 2 hours and at hourly intervals for the last 3 hours. The precise protocol was repeated on another day in the absence of the period of isometric exercise. The electrolyte excretion responses of each subject were then expressed as the ratio of the changes from basal values observed on exercise and rest days. At no time was there any difference in systolic and diastolic BP, heart rate, and rate of sodium and potassium excretion following exercise when sons of normotensive parents were compared to the sons of hypertensive parent(s). These results indicate that the retention of sodium and potassium following isometric exercise seen in patients with hypertension does not occur in subjects genetically predisposed to hypertension and suggest that the effect is a consequence of, rather than a predisposing factor to, hypertension.

Adult↗