Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although drug treatment for hypertension has been widely used for many years, overall control of this disease continues to be less than optimal. Hypertension treatment has had a positive impact on stroke rates, but rates of coronary heart disease remain high. One reason for this lack of success in treatment is that physicians have focused too narrowly on lowering blood pressure. Blood pressure is a critical element of hypertension, but many other interrelated risk factors contribute to form a complex syndrome of hypertension. Studies show that young adult subjects who do not yet have high blood pressure but do have a family history of hypertension exhibit increased incidence of other risk factors, such as high cholesterol, left ventricular dysfunction, reduced arterial compliance, and insulin resistance. These patients with "normotensive hypertension" share many characteristics with patients with fully developed hypertension, both uncontrolled and controlled. The link between these many risk factors and high blood pressure seems to lie in endothelial cell balance. If this balance is upset, elements of the hypertension syndrome start to become manifest, often before blood pressure becomes elevated. Angiotensin-converting enzyme inhibitors can restore this critical balance, improving overall arterial health and arterial compliance and thus preventing the progression of the hypertension syndrome to high blood pressure and, ultimately, target organ damage.
 ...
PMID:Why lowering blood pressure is not enough: the hypertension syndrome and the clinical context of cardiovascular risk reduction. 1172 84

A direct, continuous, and independent relation between blood pressure and the incidence of various cardiovascular events, such as stroke and myocardial infarction, is now well accepted. The increase in risk can be attributed to structural and functional changes in target organs. Central to many of these pathophysiologic processes is the renin-angiotensin system (RAS), specifically, angiotensin II. Binding of angiotensin II to angiotensin II type-1 (AT(1)) receptors produces acute vasoconstriction, leading to an increase in blood pressure. AT(1) receptor activation also contributes independently to chronic disease pathology by promoting vascular growth and proliferation, and endothelial dysfunction. These negative consequences of angiotensin II are partly counteracted by angiotensin II type-2 (AT(2)) receptor stimulation, which has favorable effects on tissue growth and repair processes. Thus, the use of selective AT(1) receptor antagonists in the treatment of hypertension has a 2-fold rationale: (1) selective AT(1) receptor blockade targets the final common pathway for all major detrimental cardiovascular actions of angiotensin II, and (2) circulating angiotensin II levels (which increase during AT(1) receptor antagonist treatment) will be free to act only at unopposed AT(2) receptors, potentially providing additional end-organ protection. Angiotensin-converting enzyme (ACE) inhibitors interrupt the RAS by preventing the conversion of angiotensin I to angiotensin II. They also increase plasma levels of bradykinin, which possesses vasodilatory and tissue-protective properties. The combination of an AT(1) receptor antagonist with an ACE inhibitor represents an appealing therapeutic strategy, because it should produce more complete blockade of the RAS, while preserving the beneficial effects mediated by AT(2) receptor stimulation and increased bradykinin levels.
 ...
PMID:The role of the renin-angiotensin system in the development of cardiovascular disease. 1183 3

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the renin-angiotensin system and exert various beneficial actions on cardiac and vascular structure and function, beyond their blood pressure-lowering effects. Randomized, controlled clinical trials have shown that ACE inhibitors improve endothelial function, cardiac and vascular remodeling, retard the anatomic progression of atherosclerosis, and reduce the risk of myocardial infarction, stroke, and cardiovascular death. Therefore, these agents are recommended in the treatment of a wide range of patients at risk for adverse cardiovascular outcomes, including those with coronary disease, prior stroke, peripheral arterial disease, high-risk diabetes, hypertension, and heart failure. ARBs are effective blood pressure- lowering and renoprotective agents and can be used in heart failure in patients who do not tolerate ACE inhibitors. The role of ARBs in the prevention of atherosclerosis and its sequelae is currently under investigation. The use of combined ACE inhibitor plus ARB therapy offers theoretical advantages over the use of each of these agents alone and is also under investigation in large, randomized clinical trials.
 ...
PMID:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in atherosclerosis. 1216 36

1. Pharmacologists should be involved in all stages of drug development. Often neglected is the final step, the clinical trials and other studies that determine clinical utility. The present article illustrates how pharmacoepidemiology can facilitate evaluation of the clinical potential of different drugs used to treat hypertension. 2. The evidence base for the drug treatment of hypertension is very strong. Large-scale outcome trials, largely based on diuretics, indicate that stroke events are prevented to the extent expected from blood pressure reduction, but there appears to be a shortfall in the prevention of coronary heart disease events. 3. On theoretical grounds, newer agents may be expected to have benefits in coronary heart disease prevention beyond blood pressure reduction. Recent trials with angiotensin-converting enzyme inhibitors and calcium channel blockers suggest no advantage over conventional drugs, but shortcomings in these studies mean that each is uninformative. 4. Observational studies based on pharmacoepidemiological principles offer an alternative approach to evaluating outcomes in treated hypertensives. 5. Evidence from the Glasgow Blood Pressure Clinic database suggest that there are outcome differences between antihypertensive agents. Angiotensin-converting enzyme inhibitor treatment is associated with a mortality advantage, whereas calcium channel blocker therapy is associated with a poorer prognosis. Preliminary findings from a primary care database support these observations. 6. Long-term follow up of a well-documented high-risk clinical population may allow detection of outcome differences not apparent in relatively short-term clinical trials. 7. Appropriate interpretation of observational data necessitates an understanding of the strengths and limitations of observational data. Clinical pharmacologists have a critical role in design and evaluation of pharmacoepidemiology studies.
 ...
PMID:Clinical trials and tribulations. 1236 84

Patients with intraatrial baffle procedure for transposition of the great arteries (TGA) have diastolic dysfunction, decreased exercise capacity, stroke volume response and elevated systemic vascular resistance (SVR) during exercise. Angiotensin-converting enzyme (ACE) inhibitors improve exercise capacity in adults with congestive heart failure by improving diastolic function and decreasing SVR. We tested the hypothesis that ACE inhibitors decrease SVR and improve exercise capacity in patients after intraatrial baffle procedure for TGA. We studied the effects of enalapril in nine patients with TGA s/p intraatrial switch (mean age, 13.8 +/- 3 years) 7 to 21 years (mean, 12 +/- 4 years) after intraatrial baffle procedure. Enalapril (0.5 mg/kg/day, maximum dosage 20 mg bid) was administered for 12 months. Patients exercised using a cycle ergometer ramp protocol (0.25 W/kg/min) before enalapril (baseline), 1 month, 6 months, and 12 months after treatment initiation. Heart rate, blood pressure, cardiac output, respiratory rate, minute ventilation, oxygen consumption (VO2), total exercise time, work, and power were measured. SVR, cardiac index, and stroke volume index (SVI) were calculated. Two-tailed paired Student's t-test was used to compare data to those of normal control patients and the patients' baseline data. Patients had lower resting heart rate, cardiac index, maximum heart rate, cardiac index (CI), SVI, VO2, exercise time, work, and power and higher maximal SVR at baseline compared to normal control patients. There was no significant difference in total exercise time, work, power, VO2 (rest/peak), SVR, SVI, and CI after 12 months of therapy compared to patients' baseline values. We conclude that short-term (<1 year) use of enalapril does not improve exercise performance in patients with TGA in whom the intraatrial baffle procedure has been performed.
 ...
PMID:Afterload reduction therapy in patients following intraatrial baffle operation for transposition of the great arteries. 1253 Apr 95

The goal of antihypertensive therapy is to provide effective treatment that can be sustained lifelong, while lowering elevated blood pressure and preventing hypertensive end-organ damage and mortality. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIAs) control blood pressure as well as other available classes of antihypertensive drugs. The ACE inhibitors have been demonstrated to reduce the incidence of stroke, reverse left ventricular hypertrophy, and improve congestive heart failure symptomatology and mortality to a similar degree as diuretics and beta-adrenergic blockers. ACE inhibitors reduce postmyocardial infarction recurrence, improve congestive heart failure symptomatology and mortality, and slow the progression of glomerular renal disease. The AIIAs reverse left ventricular hypertrophy. Several of these agents have been shown to improve congestive heart failure symptomology and mortality, to reduce the occurrence of early atherosclerotic vascular disease, and to slow the progression of renal failure in type 2 diabetes mellitus nephropathy. One AIIA has reduced the incidence of end-stage renal disease in non-insulin-dependence diabetes mellitus nephropathy over 3 years. Ideally, antihypertensive therapy should maintain or improve the patients quality of life without creating side effects or adverse laboratory effects. Among the available nine classes of antihypertensive drugs, ACE inhibitors and the AIIAs come close to meeting the description of an ideal drug. AIIAs and ACE inhibitors, two classes of antihypertensive drugs that reduce the activity of the renin-angiotensin II system, should be among the preferred first-step drugs for the treatment of hypertension.
 ...
PMID:Drugs that interrupt the renin-angiotensin system should be among the preferred initial drugs to treat hypertension. 1267 27

Angiotensin-converting enzyme (ACE) inhibitors are the first-line therapeutic agents for treating hypertension in patients with the cardiometabolic syndrome and those with diabetes. ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes and appears to improve insulin sensitivity and glucose metabolism. Several recent studies indicate that ACE inhibitor therapy reduces the development of type 2 diabetes in persons with essential hypertension, a population with a high prevalence of insulin resistance. ACE inhibitor therapy has been shown to improve surrogates of cardiovascular disease (eg, vascular compliance, endothelial-derived nitric oxide production, vascular relaxation and plasma markers of inflammation, oxidative stress, and thrombosis) and reduce cardiovascular disease, renal disease progression, and stroke. This article explores potential mechanism by which ACE inhibition reduces the development of diabetes, improves these surrogate markers, and reduces cardiovascular disease and renal disease.
 ...
PMID:Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. 1281 33

Hypertension remains one of the most unmet medical needs of this century. While many drugs are available for treating hypertension, efforts are still insufficient to find potent therapeutic agents since cause for hypertension in all patients is not the same. Angiotensin-converting enzyme inhibitors (ACEIs) have emerged as an important class of drugs in the treatment of hypertension, congestive heart failure (CHF), protenuric renal disease, myocardial infarction and stroke. This class of drugs blocks the conversion of angiotensin I to angiotensin II and prevents bradykinin breakdown. However, the lack of specificity of ACEIs leads to the frequent side effects like cough and angio-oedema. Recently developed, specific non-peptide and orally active angiotensin receptor blockers (ARBs) have become the prime therapeutics as they alone or co-administration with ACE inhibitors can control the renin angiotensin disorders. This review explores recent developments in the design, synthesis, and structural modifications of ACE inhibitors as well as angiotensin receptor blockers.
 ...
PMID:Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). 1287 Nov 64

Angiotensin-converting enzyme inhibitors and aldosterone receptor antagonists ameliorate malignant nephrosclerotic lesions of thrombotic microangiopathy in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP) without controlling hypertension. This suggests that angiotensin II (Ang II) and/or aldosterone (ALDO) plays a critical role in renal injury in this model. For evaluating their relative roles in the pathogenesis of thrombotic microangiopathy, SHRSP were adrenalectomized and infused with vehicle, Ang II, or ALDO or were sham-operated for adrenalectomy (SHAM). Saline-drinking rats were assigned to one of four groups: SHAM, adrenalectomy, adrenalectomy + Ang II (25 ng/min, subcutaneously), or adrenalectomy + ALDO (40 micro g/kg per d, subcutaneously). All SHRSP received dexamethasone (12 micro g/kg per d, subcutaneously). Adrenalectomy did not show changes in body weight, plasma creatinine, sodium and potassium, and daily urinary sodium and potassium excretion; did not prevent hypertension but prevented proteinuria (12 +/- 1 versus 49 +/- 3 mg/d; P < 0.01); and abrogated thrombotic microangiopathy and decreased plasma aldosterone (<16 versus 710 +/- 91 pg/ml; P < 0.001) compared with SHAM. Systolic BP in adrenalectomy + Ang II and adrenalectomy + ALDO (238 +/- 8 and 241 +/- 9 mmHg, respectively) was similar to SHAM. Despite Ang II infusion, proteinuria (17 +/- 9 mg/d) and thrombotic microangiopathy and plasma aldosterone (18 +/- 18 pg/ml) remained low but daily urinary excretion of sodium and potassium were not different from adrenalectomy + ALDO. Adrenalectomy + ALDO showed plasma aldosterone levels of 735 +/- 147 pg/ml; plasma potassium was lower; plasma creatinine and proteinuria (78 +/- 7 mg/d) were greater and thrombotic microangiopathy lesions were comparable to SHAM. These results demonstrate a pivotal role for aldosterone in the development of thrombotic microangiopathy, independent of hypertension.
 ...
PMID:Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP. 1287 52

We have previously described angiotensin I-converting enzyme (ACE) forms in urine of normotensive (190 and 65 kDa) and hypertensive patients (90 and 65 kDa, N-domain ACEs). Based on the results described above, experimental and genetic models of hypertension were investigated to distinguish hemodynamic and genetic influence on the generation of ACE profile in urine: Wistar-Kyoto and Brown Norway rats (WKY and BN), spontaneously and stroke-prone spontaneously hypertensive rats (SHR and SHR-SP), one kidney/one clip rats (1K1C), deoxycorticosterone acetate (DOCA) salt-treated and untreated rats, and enalapril-treated SHR (SHRen). Two peaks with ACE activity were separated from the urine of WKY and BN rats submitted to an AcA-44 column, WK-1/BN-1 (190 kDa), and WK-2/BN-2 (65 kDa), as described for urine of normotensive subjects. The same results were obtained for urine of 1K1C and DOCA salt-treated and untreated rats, analyzed to evaluate the influence of hemodynamic factors in the ACE profile in urine. The urine from SHR, SHR-SP, and SHRen presented 80 (S-1, SP-1, Sen-1) and 65 (S-2, SP-2, Sen-2) kDa ACE forms, differing from the urine profile of normotensive rats, but similar to that described for hypertensive patients. The presence of 80 kDa ACE in urine of SHR, SHR-SP, and SHRen and its absence in urine of experimental hypertensive rats (1K1C and DOCA salt) support the hypothesis that this enzyme could be a possible genetic marker of hypertension. Taken together, our results provide evidence that ACE forms with 90/80 kDa isolated from the urine of hypertensive subjects and genetic hypertensive animals behaves as a possible genetic marker of hypertension and not as a marker of high blood pressure.
 ...
PMID:N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension. 1290 Apr 33


<< Previous 1 2 3 4 5 6 7 8 9 Next >>