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Biomedical subjects

A E Doyle

Publications and source records attributed to A E Doyle.

169 records · Page 10Linked to original sources

Hypotensive action of captopril and saralasin in intact and anephric spontaneously hypertensive rats.

Intravenous injection of the converting enzyme inhibitor SQ14,225 (captopril, 2 mg/kg) reduced the blood pressure of anesthetized, spontaneously hypertensive rats (SHR) progressively over a 3-hour period. An indistinguishable fall in blood pressure occurred in SHR that were bilaterally nephrectomized 1 hour prior to injection of the converting enzyme inhibitor. In the nephrectomized animals, plasma renin activity (PRA) had fallen to less than 30% of its initial values at the time of injection. Injection of the vehicle alone had no effect on blood pressure in either anephric or intact SHR. The converting enzyme inhibitor produced no significant change in the blood pressure of either intact or anephric normotensive Wistar-Kyoto (NT-WK) rats. Infusions of Sar1-Ala8-angiotensin II (saralasin, 10 micrograms/kg-1/min-1) similarly reduced blood pressure of both intact and anephric SHR. These results indicate that captopril and saralasin lower blood pressure in the SHR by some mechanism(s) independent of the kidneys, circulating renin, or bradykinin potentiation. It is suggested that angiotensin II, locally produced at some critical tissue site(s), is involved in the maintenance of raised blood pressure in SHR.

Angiotensin II↗

Blood pressure responses of conscious normotensive and spontaneously hypertensive rats to intracerebroventricular and peripheral administration of captopril.

In conscious spontaneously hypertensive rats, intraxerebroventricular injection of captopril (2 mg/kg) resulted in a rapid hypotensive response that lasted several hours. The same dose given by intracerebroventricular injection had no significant effect on blood pressure (BP) of normotensive Wistar-Kyoto (WK) rats over 7 hours. There was no significant change in BP of conscious spontaneously hpertensive rats (SHR) in response to intracerebroventricular injection of vehicle and only a transitory fall in BP in response to intravenous injection of captopril (2 mg/kg). There was no significant differences between plasma renin activity (PRA) of conscious normotensive WKY rats and the PRA of SHR. These results suggest biochemical differences between the brains of SHR and normotensive WKY control rats. These differences could involve the brain renin-angiotensin system or other neuropeptides.

Animals↗

Comparison of beta-adrenoceptor blockers and calcium antagonists in hypertension.

The calcium antagonist drug, verapamil, was compared in double-blind, double-dummy, crossover studies with two beta-adrenoceptor blocking drugs, pindolol and labetalol. All were equally effective as antihypertensive drugs in patients with mild-to-moderate hypertension. Verapamil caused a fall in blood pressure by reducing total peripheral resistance, as judged by echocardiographic studies, and had no adverse effects on airways resistance in patients with obstructive airways disease. The favorable hemodynamic effects and absence of serious side effects suggest that verapamil may be an important advance in the treatment of hypertension.

Adrenergic beta-Antagonists↗

Response to placebo treatment in hypertension.

In essential hypertension, the blood pressure is variable, with large changes occurring in response to variations in physical and emotional stimuli. Patients given placebo tablets often have short-lived decreases in blood pressure. Placebo-controlled studies are essential for the proper evaluation of antihypertensive drugs. In longer term studies in mild hypertension, many patients given placebos have substantial decreases in blood pressure, often to normal levels, a finding that makes a period of observation desirable before commencing active treatment. Patients given placebos also have a high incidence of symptomatic side effects.

Australia↗

Erythrocyte cation cotransport and countertransport in essential hypertension.

We studied erythrocyte cation cotransport and countertransport systems in 21 and 27 patients with essential hypertension, respectively, all of whom were under 50 years of age, had a diastolic blood pressure level greater than 100 mm Hg, and had a family history of hypertension. The following parameters were normal in nearly all patients: total erythrocyte Na+ and K+ concentrations, the maximal rate (Vmax) of inward cotransport, the affinity of cotransport with Rb+ as the substrate, the net outward cotransport of Na+ ions, the passive "leak" influx of Rb,+ and the maximal rate of Li+-Na+ countertransport. Only four patients gave clearly abnormal results; in two the maximal rate of both cotransport and countertransport was double the normal values, while another two patients demonstrated a greater than twofold increase in passive "leak" influx to Rb+ ions. Most of the patients with moderate to severe essential hypertension in this Australian study were characterized by normal erythrocyte cation fluxes, but a few showed elevation of both cotransport and countertransport of cations.

Adult↗

CSF enzymes in lacunar and cortical stroke.

Cerebrospinal fluid enzyme levels of creatine kinase (CK), lactate dehydrogenase (LDH), glutamate oxaloacetate transaminase (GOT) and angiotensin converting enzyme (ACE) were studied in 40 acute stroke patients comprising 20 lacunar strokes and 20 cortical strokes. A marked elevation of at least one of the enzymes CK, GOT or LDH was seen in 80% of cases of cortical strokes. No elevation was seen in lacunar stroke with CK, GOT or ACE and only a slight elevation with LDH. Within the cortical group, there was a correlation between the site, size of infarction seen on CT scan and enzyme level. These findings may help to explain the previously noted unpredictability of rises in CSF enzymes in stroke patients. In certain instances, a study of CSF enzymes may be of use to distinguish cortical from lacunar stroke. A precise diagnosis of lacunar infarction is important for management purposes, entry into stroke treatment trials or description of new syndrome types.

Aspartate Aminotransferases↗

The management of diabetic proteinuria. Which antihypertensive agent?

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.

Aged↗