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Biomedical subjects

R M Graham

Publications and source records attributed to R M Graham.

At least 181 records · Page 10Linked to original sources
PubMed1980

Effect of indomethacin on hydralazine-induced renin and catecholamine release in the conscious rabbit.

1. The effects of hydralazine on mean arterial pressure (MAP) heart rate (HR), plasma renin activity (PRA) and plasma catecholamines were examined in conscious rabbits before and after prostaglandin synthesis inhibition with indomethacin. 2. Hydralazine (3 mg/kg. i.v.) produced a 12% decrease in MAP and significant increases in HR, PRA and plasma noradrenaline and adrenaline. 3. Indomethacin (5 mg/kg, s.c.) failed to alter significantly the control MAP, HR, PRA or plasma catecholamines but inhibited renal venous prostaglandin E2 by 56% (P less than 0.02). 4. Indomethacin inhibited the hydralazine-induced tachycardia by 24% and augmented its hypotensive effects by 6%. 5. The hydralazine-stimulated increase in PRA was also inhibited 75% (P less than 0.001) by indomethacin whereas noradrenaline and adrenaline concentrations were not significantly reduced. 6. Indomethacin inhibits hydralazine-induced renin release in the presence of elevated concentrations of plasma catecholamines; these findings suggest that renal prostaglandins function as important mediators of sympathetically-induced renin release.

Animals↗
PubMed1980

Renal function during long-term treatment of hypertension with minoxidil: comparison of benign and malignant hypertension.

We examined the effect of long-term blood pressure control on renal function in 41 patients with refractory hypertension by using minoxidil, sympathetic suppressants, and diuretics continuously for 6 months to 7 1/2 years. In 15 of 32 patients with benign hypertension, the serum creatinine concentration increased by more than 1 mg/dL, with nine of 15 requiring hemodialysis. Analysis of 1/serum creatinine versus time plots indicated that use of minoxidil delayed the onset of end-stage renal failure in some patients for up to 6 years. In the remaining 17 patients with benign hypertension, renal function remained stable with no decreases greater than 2 mg/dL. Four of nine patients presenting with malignant hypertension had marked and sustained improvement in renal function, although three initially required hemodialysis. The mean serum creatinine concentration in these four patients fell from 9.7 to 2.9 mg/dL. Thus, impressive renal functional improvement may occur with minoxidil use in some patients with malignant hypertension.

Adult↗
PubMed1980

Inhibition of hydralazine-induced renin release by indomethacin in the rat.

Renal prostaglandins (PG) appear to mediate the release of renin due to activation of the intrarenal baroreceptor and stimulation of the renal sympathetic nerves. Since the vasodilator hydralazine is thought to stimulate renin release by both of these mechanisms, we examined the effect of indomethacin, a PG synthetase inhibitor, on hydralazine-induced renin release. Hydralazine increased the serum renin levels from 3.3 +/- 0.5 to 13.7 +/- 3.1 and 41.9 +/- 2.4 ng/ml/hr at the 1 and 10 mg/kg doses, respectively. Indomethacin inhibited this hydralazine-induced renin release by 100% at the 1 mg/kg dose and 36% at the 10 mg/kg dose even though the hypotensive effect of the drug was unaltered. Indomethacin (5 mg/kg) also suppressed urinary PGE2 excretion by 60% (p < 0.001). The beta-blocker, propranolol, was as effective as indomethacin in attenuating hydralazine-induced renin release. Additionally, propranolol blocked the tachycardia associated with hydralazine and slightly enhanced the hypotensive action of the drug. When indomethacin and propranolol were combined, no further inhibition of hydralazine-induced renin release was observed. Thus, renal PG's appear to be important as mediators of hydralazine-stimulated renin release but no hydralazine-induced vasodilatation.

Animals↗
PubMed1979

Role of renal prostaglandins in sympathetically mediated renin relase in the rat.

Renal prostaglandins (PG) appear to mediate renin release due to stimulation of the intrarenal baroreceptor, but not that due to activation of the macula densa. However, as the role of PG in sympathetically mediated renin release remains unclear, a possible interrelationship between these factors was examined in conscious rats. Hydralazine increased the serum renin levels from 3.1+/-0.8 to 16.7+/-3.0 ng/ml per h at a dose of 1 mg/kg. Indomethacin (5 mg/kg) suppressed urinary PGE(2) and PGF(2alpha) excretion by 89 and 74%, respectively, arachidonate hypotension by 82%, and inhibited the elevated renin levels from hydralazine by 100% without altering the hypotensive effect of the drug. Another PG synthetase inhibitor, meclofenamate, was also effective in attenuating hydralazine-induced renin release, urinary PGE(2) and PGF(2alpha) excretion, and arachidonate hypotension. Isoproterenol, a nonselective beta-adrenergic agonist, increased heart rate, lowered blood pressure, and also stimulated the release of renin when administered intraperitoneally. However, intrarenal infusion of the drug only resulted in increased renin release. Indomethacin inhibited isoproterenol-induced renin release by 66 and 67%, respectively, without altering the hemodynamic effects associated with the intraperitoneal administration of the drug. The selective beta(1) agonist, H133/22, increased the release of renin and heart rate in a dose-related manner without altering blood pressure. H133/22-induced renin release was inhibited by 80% by indomethacin pretreatment. Finally, intrarenal infusions of dibutyryl cyclic AMP (3 mg/kg per min) increased the serum activity from 4.1+/-0.2 to 20.4+/-3.9 ng/ml per h without altering mean arterial pressure. Indomethacin inhibited this renin response to dibutyryl cyclic AMP by 96%. Thus, renal PG appear to be important mediators of sympathetically stimulated renin release acting as a site distal to the beta-adrenergic receptor.

Adrenergic beta-Agonists↗
PubMed1977

Influence of dosage and dietary sodium on the first-dose effects of prazosin.

The effects of the first dose of prazosin were assessed in hypertensive patients on different sodium intakes. Patients received 250, 100, or 30 mmol sodium per 24 hours for a week before taking 2 mg or 0-5 mg prazosin. The acute effects of prazosin on blood pressure and pulse rate were milder with a high sodium intake. On the 100-mmol intake symptomatic postural hypotension occurred in five out of seven patients given 2 mg prazosin and in two out of four given a 0-5-mg dose, whereas those taking 2 mg or 0-5 mg and a 250-mmol sodium intake experienced no postural symptoms. These findings indicate that particular care should be taken in starting prazosin treatment in sodium-depleted patients.

Adult↗
PubMed1977

The effect of mental arithmetic in normotensive and hypertensive subjects, and its modification by beta-adrenergic receptor blockade.

1 The effects of a 5-min period of sustained mental arithmetic upon blood pressure and heart rate were determined in several groups of healthy subjects and hypertensive patients. 2 The arithmetic produced significant increases in heart rate and blood pressure (both systolic and diastolic) in both normotensive and hypertensive subjects. 3 The blood pressure changes were neither attenuated nor enhanced by the prior administration of basis. 4 In subjects habituated to the test the heart rate increase was unaffected by the drugs, but in those less familiar with the test it was usually attenuated. 5 Although the beta1-adrenoceptor selective blocker, metoprolol, caused decreases in baseline values for blood pressure and heart rate similar to those observed with the use of the two non-selective blockrs, it was shown in a double-blind crossover comparison with propranolol that the haemodynamic changes provoked by the mental arithmetic were not less in the presence of beta1-receptor blockade than when both beta1- and beta2-receptors were blocked. 6 These findings suggest that, during beta2-adrenoceptor blockade, the haemodynamic effects of minor mental stress are not exaggerated because of uncompensated alpha-receptor mediated vasoconstriction, such as occurs following adrenaline infusion.

Adrenergic beta-Antagonists↗
PubMed1977

The use of clonidine by intramuscular injection in the treatment of hypertension.

Clonidine (Catapres) administered intramuscularly in a dose of 150 microng produced a satisfactory reduction in blood pressure in 13 of 16 hypertensive patients. Its effect occurred within five minutes, was maximal at 75 minutes and persisted for five hours. In six patients who received two doses (150 microng and 300 microng), the response was shown to be dose-related. No serious side effects were noted. Intramuscular administration of clonidine thus appears to be safe and effective. It has a place in the management of uncontrolled hypertension when a rapid reduction in blood pressure is undesirable and in the maintenance of blood pressure control when oral therapy cannot be tolerated.

Adult↗
PubMed1977

Alpha blocking action of the antihypertensive agent, prazosin.

The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1977

Mechanism of the hypotensive action of prazosin.

The mechanism of action of prazosin was studied in anesthetized rats by comparison with the peripherally-acting anti-hypertensive agents, indoramin, hydralazine and diazoxide. Hydralazine and diazoxide retained full hypotensive potency after ganglionic blockade with pentolinium or alpha adrenoceptor blockade with phentolamine. Hydralzaine and diazoxide also attenuated angiotensin II pressor responses. In contrast, the hypotensive activity of prazosin was completely abolished, and that of indoramin was almost abolished by either pentolinium or phentolamine pre-treatment. Neither prazosin nor indoramin caused impairment of angiotensin II responsivity, but each was shown to possess alpha adrenoceptor blocking properties. Both agents antagonized the pressor action of norepinephrine and reversed responses to epinephrine. Thus, while hydralazine and diazoxide act directly upon the vasculature by mechanisms independent of sympathetic vasomotor tone, prazosin, like indoramin, acts as an alpha adrenoceptor blocking agent.

Angiotensin II↗
PubMed1976

Experience with prazosin in the treatment of patients with severe hypertension.

The efficacy and safety of prazosin, a new vasodilator antihypertensive agent, used mainly in combination with other hypotensive medication, was evaluated in 50 hypertensive patients, 28 of whom had left ventricular hypertrophy and 28 of whom had renal impairment. In 44 cases this agent was introduced because of an inadequate response to, or side effects from other agents. In 38 cases (76%) there was a satisfactory response, the diastolic blood pressure being reduced to 100 mm Hg or less. The blood pressure of the whole group of 50 patients was reduced by an average of 31/20 mm Hg. The mean duration of therapy was 6-6 months. Side effects necessitating withdrawal of prazosin occurred in only three cases. Plasma renin activity was reduced to 25% of the control value in a group treated with prazosin alone.

Adult↗
PubMed1976

Surgical intervention in severe and complicated renal hypertension: Report of the Sydney Renal Hypertension Group (1969-75).

1. A prospective study was undertaken in seventy-eight patients with renal hypertension (fifty-eight with renovascular disease and twenty with renal parenchymal disease), after their presentation to an advisory group as possible candidates for surgical management. 2. Vascular repair and/or nephrectomy were performed in forty-four patients, and the remainder were treated with anti-hypertensive drugs. The control of blood pressure was then assessed over periods of 6-70 months. 3. Of the patients treated surgically, fifteen (34%) were normotensive without medication and fifteen had improved blood pressure control; the morbidity rate was the same as in the medically treated group, but mortality was lower and blood pressure control was better, particularly among patients under 40 years of age. 4. Surgery undertaken primarily to conserve renal function was beneficial in four of nine patients with bilateral renal artery stenosis and severe, progressive uraemia. 5. The blood pressure response to surgical correction of unilateral renal lesions was predicted correctly by the preoperative renal vein renin ratio in fifteen of eighteen cases.

Adult↗