Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of insulin on Ca2+ regulation of vascular smooth muscle cells (VSMC) in hypertension, the effect of insulin on Ca2+ transport and intracellular free calcium concentration ([Ca2+]i) was measured in cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured VSMC. The stimulatory effects of insulin were completely inhibited by diltiazem, and partially by H-7, TMB-8, and 5-N,N(hexamethylene)amiloride (HMA), but not by W-7 or trifluoroperazine. Insulin-sensitive 45Ca uptake of SHR VSMC was significantly smaller than that of WKY VSMC. Insulin-sensitive increase in [Ca2+]i of SHR VSMC was also smaller than that of WKY VSMC. It is concluded that insulin increases 45Ca uptake, leading to an increase in [Ca2+]i, presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release, or protein kinase C mediated mechanisms in cultured VSMC. A blunted response of insulin-sensitive Ca2+ uptake and [Ca2+]i in SHR VSMC suggests the differential regulation of Ca2+ transport in response to insulin in primary hypertension.
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PMID:Decreased insulin-sensitive Ca2+ transport in cultured vascular smooth muscle cells from spontaneously hypertensive rats. 128 39

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.
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PMID:Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation. 128 83

It is now recognized that left ventricular hypertrophy (LVH), often associated with hypertension, is itself a risk factor for coronary disease in the elderly. Although many agents are capable of controlling blood pressure, the ability of these agents to induce regression of left ventricular (LV) mass, and the effect of regression on diastolic relaxation and contractile indices in the elderly are less well known. Our study compared the ability of the calcium blocker, verapamil, and the beta-blocker, atenolol, to both control blood pressure (BP) and to induce regression of LV mass in older hypertensives. In addition, the influence of regression on resting diastolic filling and on cardiac output and ejection fraction during rest and mild upright bicycle exercise were determined. Forty-two hypertensives 60 years of age or above, without evidence of ischemic disease underwent 2-D echocardiographic evaluation of LV mass and gated blood pool scan determination of early diastolic filling, cardiac output and ejection fraction. They were then randomized to receive verapamil or atenolol during a four-week titration period so as to achieve a BP of less than 160/90 mm Hg. If BP was not controlled with either agent, chlorthalidone was added. Individuals whose BP was controlled continued on the protocol for six months. At that time, the echocardiographic and gated blood pool studies were repeated both on and after subsequent withdrawal of the study medications. Twenty-one patients were randomized to receive verapamil and 21 patients to receive atenolol. Blood pressure control was achieved with verapamil alone in 18 patients, but with atenolol alone in only 8 patients (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular mass regression in elderly hypertensives. 128 8

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

The calcium antagonist verapamil has been demonstrated to be effective in reducing hypertension in patients in whom sodium intake was not restricted. The present study evaluated the effect of verapamil in reducing hypertension in patients with chronic renal failure on low or high sodium diets. Also, the present study evaluated the effect of verapamil on proteinuria in chronic renal failure patients who were administered a normal and low protein diet. The results reveal that verapamil-SR 240 mg daily is effective in reducing hypertension in patients with chronic renal failure and the effect of verapamil is equal in patients on a high or low sodium intake. In addition, verapamil-SR 240 mg daily is effective in maintaining reduced proteinuria in chronic renal failure patients on low protein diet and may prevent proteinuria in such patients on a normal protein diet. Therefore, verapamil-SR 240 mg daily appears to be an excellent choice for the treatment of hypertensive chronic renal failure patients.
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PMID:The antihypertensive effect of verapamil in patients with chronic renal failure. 128 13

Whether or not some classes of antihypertensive drugs have an anti-atherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies, primarily involving calcium antagonists. Most experimental investigations have shown a significant anti-atherogenic action of calcium antagonists, but only when the drug is administered simultaneously with the atherogenic stimulus (mainly cholesterol feeding). When the drug is administered weeks or months after the beginning of the atherosclerotic process (as in the Watanabe heritable hyperlipidemic rabbit), with a single exception, no antiatherogenic effect has been shown. The few clinical studies completed so far have been on symptomatic coronary patients. Little is known of the effects of calcium antagonists on asymptomatic lesions in the carotid arteries of hypertensive patients, in whom carotid plaques can be identified and followed-up by non-invasive ultrasound techniques. However, two such trials are underway. The Verapamil in Hypertension Atherosclerosis Study (VHAS) is an ongoing randomized trial, comparing the antihypertensive efficacy of verapamil 240 mg SR with chlorthalidone 25 mg in 1,464 essential hypertensives aged 40-65 years. In a random subgroup of patients (500), who will be followed for three years, B-mode ultrasonography is being carried out blindly to evaluate the effect of the two drugs on carotid wall thickness and on carotid plaques, when present. Preliminary baseline data are available in 440 of the hypertensive patients in whom ultrasound investigation was performed. The mean (+/- SD) age of these patients was 53.7 +/- 6.9 years; 32.5% had echocardiographically normal carotid walls; 30.9% showed intima-media thickening; and 36.6% had one or more plaques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atherosclerosis and calcium antagonists: the VHAS. The Verapamil-Hypertension Atherosclerosis Study (VHAS) Investigators. 128 14

Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65-85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum potassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking.
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PMID:Treatment of hypertension in the elderly--what have we learned from the recent trials? 129 75

All major randomized trials of antihypertensive therapy have used cardiovascular events as endpoints. This approach has provided important information, but has also led to a few inappropriate conclusions. In particular, no sound information is available on the ability of antihypertensive therapy to prevent the cardiovascular lesions upon which events are superimposed. However, particularly in mild to moderate hypertensives, the primary goal of therapy is prevention of cardiovascular lesions rather than prevention of premature death. Sensitive and quantitatively reliable methods for evaluation of organ damage in hypertension are now available. For instance, the quantitative evaluation of coronary plaques has recently been employed in therapeutic trials of coronary artery disease; non-invasive methods (such as quantitative ultrasonography of carotid artery walls) can be employed in large trials of antihypertensive therapy to answer the question whether some class of antihypertensive drugs, such as calcium-antagonists) may be more effective in prevention and/or regression of atherosclerotic plaques than traditional antihypertensive agents.
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PMID:[Hypertension and cardiovascular damage]. 129 4

Isradipine (Lomir) a new dihydropyridine calcium antagonist was evaluated for its efficacy, tolerability and safety among mild to moderate Tanzanian hypertensives. Twenty nine patients (7 males and 22 females), mean age 42.7 +/- 8.5 years entered active treatment phase, of the 16 week open label therapeutic trial. A mean decrease from base line in supine systolic blood pressure (SBP) of 17.6 mmHg (p < 0.001) and diastolic blood pressure (DBP) of 13.5 mmHg (p < 0.001) were achieved at the end of the study period. The corresponding changes from base line in standing SBP and DBP were 18 mmHg (p < 0.001) and 13.5 mmHg (p < 0.001) respectively. The efficacy was excellent or good in 84% and fair or none in 16% of the study patients. The tolerability of the drugs was excellent or good in 88.8% of patients, fair in 7.4% and bad in 3.8%. The mild side effects included headache, palpitations, tiredness and nocturia. But these improved with continued treatment. Isradipine (Lomir) at a dose of 1.25mg to 2.5mg twice daily is effective, safe and tolerable in mild to moderate hypertension.
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PMID:Efficacy, tolerability and safety of isradipine (Lomir) in the treatment of mild to moderate Tanzanian hypertensives. 129 33

Hypertension is associated with cardiac hypertrophy, which is a structural adaptation of the heart in order to attenuate the systolic stress on the left ventricle. As cardiac myocytes cannot divide, they increase in mass and volume, probably by activating second messengers and proto-oncogenes involved in cellular differentiation and proliferation. Various mechanisms, such as pressure overload and angiotensin II (Ang II), have been proposed to trigger cardiocyte growth and left-ventricular hypertrophy (LVH). In both cases, activation of second messenger routes which increase the intracellular calcium concentration, protooncogene expression, and protein synthesis have been demonstrated. Ang II also facilitates the action of another trophic agent for cardiocytes, which is noradrenaline (NA). In addition, the prevention and reversal of LVH by inhibitors of angiotensin-converting enzyme (ACE) suggests a key role for Ang II. However, no conclusive evidence has demonstrated the role of a single pathophysiologic factor in LVH. Therefore, it is more attractive to suggest a link between high blood pressure, renin-angiotensin and other vasoactive systems, such as the adrenergic system, which might together lead in a synergistic way to cardiac hypertrophy.
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PMID:Mechanisms of cardiac growth. The role of the renin-angiotensin system. 129 8


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