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Biomedical subjects

A E Doyle

Publications and source records attributed to A E Doyle.

At least 19 recordsLinked to original sources
PubMed1995

Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes.

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.

Albuminuria↗
PubMed1994

The paradoxical effect of diet commercials on reinhibition of dietary restraint.

Although many studies have explored the mechanism by which dietary restraint becomes disinhibited, few have examined how restraint is restored or "reinhibited." Using a taste test with preload design, we showed a sad movie clip interrupted by diet-related commercials, neutral commercials, or no commercials to women with high and low restraint scores. We predicted that images of successful dieting would foster reinhibition. Results, however, revealed the opposite: high restrained eaters who viewed the diet-oriented commercials ate more than other subjects. We interpret these data as suggesting that diet-related images act as additional disinhibitors and view our results in light of research linking ego threat to dietary disinhibition (Heatherton, Herman, & Polivy, 1991).

Advertising↗
PubMed1993

A review of the short-term benefits of antihypertensive treatment with emphasis on stroke.

Hypertension is the major underlying risk factor for stroke, and the risk of stroke increases proportionally to the rise in blood pressure. In the elderly, systolic hypertension increases the risk of stroke. Stroke in hypertensive patients may be due to Charcot-Bouchard aneurysm, to atherosclerosis of the extracranial and major cerebral arteries, or to embolism as a result of cardiac disease. Reduction of blood pressure greatly reduces the risk of stroke in severe, mild-to-moderate, and isolated systolic hypertension. The reduction in stroke risk occurs up to a year after the onset of treatment and appears to persist thereafter. The use of dihydropyridine calcium antagonists may confer further benefits in addition to those related to blood pressure reduction as these agents block the influx of calcium into ischemic brain cells, thereby limiting the extent of the infarction. However, although these effects have been impressive in experimental models, there is as yet no convincing evidence of this effect in clinical studies.

Aged↗
PubMed1993

Angiotensin II, sodium, and cardiovascular hypertrophy in spontaneously hypertensive rats.

Angiotensin II (Ang II) may cause cardiovascular hypertrophy as a consequence of increased blood pressure or possibly by direct trophic actions. To dissociate Ang II and blood pressure in young spontaneously hypertensive rats (SHR), we used sodium loading during angiotensin converting enzyme inhibitor treatment. Animals were treated between 6 and 10 weeks of age with perindopril to lower Ang II and blood pressure, or with perindopril and 1% saline drinking fluid or perindopril and aldosterone infusion to lower Ang II but maintain high blood pressure. Blood pressure, heart weight, and media/lumen ratio of mesenteric resistance arteries were studied while rats were on treatment at 10 weeks of age and 15 weeks after treatment at 25 weeks of age. Perindopril lowered blood pressure and inhibited the development of cardiovascular hypertrophy. Saline or aldosterone restored high blood pressure during perindopril treatment and resulted in increased heart weight/body weight and resistance artery media/lumen ratios in direct proportion to the elevation of blood pressure. Because increased structure occurred despite perindopril treatment, we conclude that direct trophic actions of Ang II are not essential for the development of cardiovascular hypertrophy in young SHR and that the antitrophic actions of angiotensin converting enzyme inhibitors depend more on changes in blood pressure than on Ang II. However, restoration of blood pressure and structure by sodium during perindopril treatment raises the possibility that the design of the cardiovascular system and blood pressure may depend indirectly on Ang II through effects on sodium metabolism.

Angiotensin II↗
PubMed1993

The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy.

The effect of the angiotensin-converting enzyme inhibitor, perindopril, on functional and structural parameters of diabetic nephropathy has been compared with triple therapy (hydralazine, reserpine, and hydrochlorothiazide) in normotensive, STZ-induced diabetic Sprague-Dawley rats. Animal groups included control rats, diabetic rats treated with perindopril, diabetic rats receiving triple therapy, and untreated diabetic rats. Treatment was continued for 32 wk. Blood pressure reduction and severity of diabetes, as assessed by body weight and glycemic control were similar with both drug regimens. A similar rise in plasma renin activity occurred in the two groups receiving antihypertensive drugs, whereas the perindopril but not the triple therapy group had suppressed plasma angiotensin-converting enzyme activity. No significant difference was observed in renal function among the four groups. Diabetes was associated with a progressive increase in albuminuria, but this rise was ameliorated by both perindopril and triple therapy. No significant difference was noted in albuminuria between triple therapy and perindopril-treated diabetic rats. Diabetes was associated with glomerular basement membrane thickening, mesangial expansion, and glomerular volume. No glomerular ultrastructural parameter was affected by antihypertensive drugs. No specific benefit of angiotensin-converting enzyme inhibition over triple therapy could be detected in this normotensive model of diabetic nephropathy.

Analysis of Variance↗
PubMed1992

Antihypertensive therapy in a model combining spontaneous hypertension with diabetes.

We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology.

Albuminuria↗
PubMed1992

Role of angiotensin-converting enzyme inhibitors in preventing or reducing end-organ damage in hypertension.

Angiotensin-converting enzyme inhibitors have been shown to be effective therapy for hypertension, and also for severe congestive heart failure, whether due to hypertension or to other causes. The reduction in cardiac hypertrophy that follows the use of these drugs is undoubtedly due in part to their favorable hemodynamic effects of reducing peripheral resistance and inducing venodilation. The same factors reduce cardiac dilation and left ventricular remodeling after myocardial infarction. The prevention of the hemodynamic effects of angiotensin II (Ang II) is probably the major factor in preventing end-organ damage, but there are some indications that Ang II may have an effect independent of blood pressure in promoting vascular hypertrophy. The separation of vasoconstrictor effects from any metabolic effects of Ang II is not easy, and final elucidation of the mechanisms involved is not yet available.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Hypertension and vascular disease.

The use of antihypertensive drug treatment has altered the natural history of hypertension. Whereas congestive heart failure, cerebral hemorrhage, and renal failure were the major complications of untreated severe hypertension, myocardial infarction and thrombotic stroke have emerged as major problems in treated hypertensive patients. None of the major therapeutic trials in hypertension have provided evidence that reducing blood pressure reduces the risk of atherosclerotic complications of hypertension. Hypertension certainly aggravates the severity of atheromatous lesions in experimental animals, and may do so in humans. However, atherosclerosis is more closely related to disturbances in lipoprotein metabolism than to other factors. The common finding that serum cholesterol is raised in hypertensive patients may be due to atherosclerosis being the primary lesion, and hypertension a secondary complication rather than hypertension being the primary lesion.

Antihypertensive Agents↗
PubMed1991

Hypertension and vascular disease.

The use of antihypertensive drug treatment has altered the natural history of hypertension. Whereas congestive heart failure, cerebral hemorrhage, and renal failure were the major complications of untreated severe hypertension, myocardial infarction and thrombotic stroke have emerged as the major problems in treated hypertensives. None of the major therapeutic trials in hypertension have provided evidence that reducing blood pressure reduces the risk of atherosclerotic complications of hypertension. Hypertension certainly aggravates the severity of atheromatous lesions in experimental animals and, thus, may do so in humans. However, atherosclerosis is more closely related to disturbances in lipoprotein metabolism than to other factors. The common finding that serum cholesterol is raised in hypertensive patients may be due to atherosclerosis being the primary lesion, with the hypertension as a secondary complication rather than the primary lesion.

Arteriosclerosis↗
PubMed1991

Sir Horace Smirk. Pioneer in drug treatment of hypertension.

Sir Horace Smirk deserves much of the credit for establishing the benefits of reducing blood pressure. He was one of the main early proponents of the idea that it was the raised intra-arterial pressure itself that caused many of the cardiac and vascular complications of hypertension. His training in both pharmacology and internal medicine enabled him to devise practical methods for successful treatment of hypertension with ganglion blocking drugs such as hexamethonium. The major clinical benefits that followed such drug treatment proved a great stimulus to the development of drugs with fewer disadvantages and to widespread acceptance of the beneficial effects of antihypertensive drug treatment.

Antihypertensive Agents↗
PubMed1991

Age-related effects of 5-HT2 antagonists.

Ketanserin, an S2 antagonist, has been shown to be an effective antihypertensive drug. Carefully controlled clinical trials have demonstrated that ketanserin is as effective as both metoprolol and thiaside diuretics in reducing blood pressure. However, unlike the beta-blocking drug metoprolol and the diuretics, the response rate to ketanserin is significantly greater in older patients, reflecting perhaps the greater vasoconstrictor effects of 5-hydroxytryptamine in patients with atherosclerotic disease. This enhanced vasoconstrictor response to serotonin in elderly patients may be matched by an increased effect on platelet aggregation, which is also blocked by ketanserin. There is very suggestive evidence from the PACK study that ketanserin may reduce vascular thrombotic episodes in patients with extensive atherosclerosis. This unique characteristic, combined with effectiveness as an antihypertensive agent, makes ketanserin a particularly useful drug in the treatment of elderly patients with hypertension and vascular disease.

Adult↗
PubMed1990

Serotonin antagonists and vascular protection.

There is very suggestive evidence for a role of serotonin release from platelets in the mechanisms for platelet aggregation, arterial thrombosis, and arterial spasm. These effects are mediated via the 5HT2 receptor and are specifically antagonized by ketanserin. The recently published PACK study was a randomized controlled trial of the effects of ketanserin in patients with intermittent claudication. The purpose of the trial was to discover whether ketanserin treatment would reduce the incidence of atherosclerotic complications such as myocardial infarction or stroke. An unexpected adverse interaction between ketanserin and potassium-losing diuretics was observed, causing an excess of deaths in the group taking this combination of drugs. The "intention-to-treat" analysis showed no overall difference between ketanserin and placebo in terms of cardiovascular complications. Withdrawal of patients taking potassium-losing diuretics left insufficient numbers of patients in the study to answer the original question. However, the "on-treatment" analysis excluding those taking the combination suggested strongly, although did not prove, that ketanserin reduced thrombotic episodes by about 25%. It is concluded that the risks of interactions between many drugs and potassium-losing diuretics make the use of the latter undesirable. Further studies on ketanserin, possibly combined with thromboxane A2 inhibitors, seem highly desirable.

Animals↗
PubMed1990

Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy.

We compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted.

Administration, Oral↗
PubMed1990

Stroke as a clinical problem in hypertension.

Stroke is a major clinical problem in hypertension. Cerebral hemorrhage has become considerably less frequent since treatment of hypertension has become more widely used. Antihypertensive treatment has also reduced the incidence of lacunar stroke, which is a result of hypertensive vascular disease of small arteries. Cortical cerebral infarction due to embolus from extracranial arterial atheromatous plaques is now the most common clinical cause of stroke. Drug treatment for hypertension has probably not reduced the incidence of this type of stroke. Cigarette smoking is also associated with an increased incidence of stroke; the incidence is related to the amount smoked, and former smokers continue to be at increased risk for up to 10 years.

Animals↗
PubMed1989

Smoking as a risk factor for cerebral ischaemia.

To assess whether a rigorous clinical classification, based on computerised tomography, of patients with cerebral ischaemia would identify subgroups at higher or lower risk with respect to cigarette smoking habits, a case-control study was carried out on 422 cases of first-episode cerebral ischaemia matched for age and sex with 422 community-based neighbourhood controls. Patients with ischaemic stroke due to extracranial or intracranial vascular disease were at higher risk from smoking than has previously been reported for stroke (relative risk 5.7, 95% confidence interval 2.8, 12.0) whereas those with stroke due to cardiac emboli had no excess risk associated with smoking (relative risk 0.4 [0.1, 1.8]). After cessation of smoking, the relative risk declined gradually over 10 years, at the end of which time a significant risk was still evident. This finding may imply that the risk incurred by smoking is due mainly to atheroma formation, rather than transient haematological effects. Exposure to smoking by a spouse was an independent risk factor for the whole group of cerebral ischaemia patients (relative risk 1.7 [1.1, 2.6]), but this was not so for smoking by either parent (relative risk 1.2 [0.8, 1.8]). These findings suggest that smoking is a more potent risk factor for the most common form of ischaemic stroke than has previously been appreciated. The persistent nature of the risk even after cessation of smoking and the possible risk associated with passive exposure strengthens public health arguments against smoking.

Adult↗