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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human mesangial cells in culture proliferate in response to platelet-derived growth factor (PDGF) and thrombin. Both of these agents also induce changes in cytosolic calcium that are dependent on both mobilization of intracellular calcium and influx of extracellular calcium. We hypothesized that calcium channel blockers, by preventing influx of extracellular calcium, may inhibit proliferation induced by these mitogens. We found that three different calcium channel blockers, diltiazem, nifedipine, and verapamil, were able to significantly inhibit [3H]thymidine incorporation into human mesangial cells induced by either PDGF or thrombin. The inhibitory effect of these agents was significant at 10(-5) M. The calcium channel blockers also attenuated the increases in cell number and percentage of labeled nuclei induced by these mitogens. In contrast, dantrolene, an inhibitor of intracellular calcium mobilization, had no significant effect on [3H]thymidine incorporation by PDGF or thrombin. Finally, the calcium channel agonist, Bay K 8644 was found to stimulate [3H]thymidine incorporation into mesangial cells. Although the mechanisms for these effects of calcium channel blockers are not proven, these studies suggest that influx of extracellular calcium is an important signal in mitogen-induced mesangial proliferation and that these agents can be beneficial in preventing or attenuating renal diseases characterized by proliferation of these cells.
Hypertension 1990 Feb
PMID:Inhibition of human mesangial cell proliferation by calcium channel blockers. 168 25

Recent studies in animal models suggest that glomerular capillary hyperperfusion and hypertension, rather than ischemia, cause renal injury. Interventions that control glomerular capillary hypertension may protect against progressive injury, even in the presence of continued systemic hypertension. In the absence of systemic hypertension, diabetes mellitus is a prominent clinical example of glomerular hypertension. Animal studies have shown that glomerular hemodynamic abnormalities, especially elevations in glomerular pressure, play an important role in the pathogenesis of diabetic glomerulopathy. A number of clinical observations suggest that angiotensin converting enzyme (ACE) inhibitors may delay the progression of diabetic nephropathy by their effects on renal hemodynamics. In experimental animals, comparisons between calcium channel blockers and ACE inhibitors have shown the latter to be more effective in protecting the kidneys. Preliminary clinical studies indicate that ACE inhibitors may have advantages in preserving renal function in hypertensive and diabetic patients with renal failure.
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PMID:Renal effects of converting enzyme inhibitors in hypertension and diabetes. 169 12

There have been many changes in the treatment of hypertension over the past few decades. The Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC) has published four reports since 1977. The first three highlighted diuretic therapy as the main ingredient of stepped care for hypertensive patients. In the fourth report, this position has been revised to a patient-oriented, or individualized, approach. The shift reflects the results of many studies on hypertensive patients treated with a variety of approaches and drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatholytics, and calcium channel blockers. After analyzing the patient's history, physical, and laboratory findings, the report recommends making choices from the various agents, based on patient demographics, sequelae, concomitant diseases, and other risk factors such as cholesterol levels.
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PMID:JNC-IV and the evolution of stepped care to individualized treatment of hypertension. 169 13

Mortality resulting from coronary artery disease and sudden death has not been significantly reduced by the use of antihypertensive medications in patients with hypertension, despite evidence that hypertension is a major risk factor for myocardial infarction. One possible reason is that the drugs used may have adverse metabolic effects that negate the beneficial effect of lowering blood pressure. Diuretics and beta-blocking agents produce a wide range of biochemical or metabolic alterations-e.g., changes in plasma potassium and in lipoprotein profiles. In general, fewer or less marked alterations are associated with the use of angiotensin-converting enzyme inhibitors, alpha-adrenergic blockers, and slow calcium channel blocking drugs. The effects of these agents alone and in combination and their potential relationship with coronary adverse events are reviewed. Although the clinical relevance of these alterations has yet to be fully determined, it is rational to suggest that given or current knowledge, the antihypertensive agent selected for use should be an effective, well-tolerated drug with a minimum of adverse biochemical or metabolic effects.
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PMID:Metabolic effects of various antihypertensive agents. 169 29

In a recent study in which metabolic characteristics of newly detected obese and nonobese hypertensive subjects were compared with those of normotensive subjects, insulin sensitivity was decreased, fasting insulin values and insulin values after an intravenous glucose tolerance test (IVGTT) were increased, and fasting and IVGTT glucose values were increased in both hypertensive groups. Furthermore, adverse alterations in lipid profile variables were found in the hypertensive groups when compared with the normotensive group. The effects of various antihypertensive agents on these metabolic variables have been assessed in prospective trials. Treatment with the beta 1-selective blocking agents metoprolol and atenolol was associated with decreased insulin sensitivity and increased fasting values of insulin and glucose. There were also indications of a suppressive effect on insulin secretion during IVGTT, as well as an increase in serum triglycerides and a decrease in serum high-density lipoprotein cholesterol. Hydrochlorothiazide treatment was associated with a decrease in insulin sensitivity and an increase in blood glucose concentrations. In addition, hydrochlorothiazide increased total cholesterol, particularly the low-density lipoprotein fraction. The calcium channel blocker diltiazem did not appear to produce any negative metabolic effects. Treatment with the angiotensin converting enzyme inhibitor captopril resulted in increased insulin sensitivity with no adverse effects on lipids. All of the agents reduced blood pressure to a similar degree. These findings, and those of other studies, suggest that captopril and diltiazem offer advantages over the other agents with regard to effects on risk factors for coronary artery disease other than hypertension. Unlike diltiazem, captopril improves insulin sensitivity and this may prove to be important.
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PMID:Insulin sensitivity in newly detected hypertensive patients: influence of captopril and other antihypertensive agents on insulin sensitivity and related biological parameters. 169 31

This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats.
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PMID:Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats. 169 54

Antihypertensive therapy reduces cardiovascular risk in patients with malignant hypertension, but has not yet been shown to reduce risk in patients with mild to moderate hypertension. The lack of significant coronary prevention in the latter group, in large-scale trials, may have resulted from methodologic problems, statistical limitations, the adverse effects of antihypertensive medications, or failure to recognize the prognostic importance of concomitant regression of left ventricular hypertrophy. To date, primary prevention studies have focused on the use of beta-blockers and diuretics, both of which may have adverse metabolic effects and neither of which is capable of modifying left ventricular hypertrophy. Future research should be directed toward evaluating coronary prevention in patients with nonmalignant hypertension who have been treated with newer agents, such as calcium channel blockers and angiotensin-converting enzyme inhibitors, each of which has been shown to regress left ventricular hypertrophy and not to have adverse metabolic effects.
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PMID:Antihypertensive therapy and coronary prevention. 170 11

Hypertension is a major disease in the black population of sub-Saharan Africa and the U.S. The prevalence of hypertension varies from 1-30% of the adult population. Differences in blood pressure (BP) between black and white patients have been documented. In this review, genetic, endocrine, and environmental characteristics, renal physiology, and cardiac function are reviewed. Racial differences in renal physiology and socioeconomic status seem to account for BP differences. Black hypertensive patients in sub-Saharan Africa are prone to cerebral hemorrhage, malignant hypertension leading to uremia, and congestive heart failure, whereas coronary artery disease is uncommon. Responses to hypotensive agents like beta-blockers and angiotensin-converting enzyme inhibitors are poor unless these agents are combined with a thiazide diuretic. Black hypertensive patients respond best to diuretics, vasodilators, or calcium channel blockers. A profiled approach to the treatment of hypertension is suggested.
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PMID:Perspectives of hypertension in black patients: black vs. white differences. 170 30

Guanine nucleotide binding proteins couple a wide variety of receptors to ion channels via both "direct" or membrane-delimited and "indirect" second messenger-mediated pathways. This tutorial summarizes current approaches to defining the mechanisms of guanine nucleotide binding protein-mediated ion channel activation. Two well-characterized ion channels in the heart, namely, the beta-adrenergic receptor-activated calcium channel and the muscarinic receptor-activated potassium channel, are used to illustrate the criteria that can distinguish between direct and indirect guanine nucleotide binding protein-transduced pathways.
Hypertension 1991 May
PMID:G protein-mediated ion channel activation. 170 43

Nifedipine antagonises influx of calcium through cell membrane slow channels, and sustained release formulations of the calcium channel blocker have been shown to be effective in the treatment of mild to moderate hypertension and both stable and variant angina pectoris. Preliminary findings also indicate that these formulations are effective in the treatment of Raynaud's phenomenon and hypertension in pregnancy, and that they reduce the frequency of ischaemic episodes in some patients with silent myocardial ischaemia. The exact mechanism of action of nifedipine in all of these disorders has not been defined. However, its potent peripheral and coronary arterial dilator properties, together with improvements in oxygen supply/demand, are of particular importance. A major goal of sustained release therapy is to permit reductions in the frequency of nifedipine administration, preferably to once daily, and thus improve patient compliance. Two new once-daily formulations--the nifedipine gastrointestinal therapeutic system (GITS) and a fixed combination capsule comprising sustained release nifedipine 20 mg and atenolol 50 mg--have exhibited marked antihypertensive efficacy. The GITS preparation has also been used effectively in the treatment of stable angina pectoris, and both formulations appear to be well tolerated. Sustained release nifedipine formulations are generally better tolerated than their conventionally formulated counterparts, particularly with regard to reflex tachycardia. Adverse effects seem to be dose related, are mainly associated with the drug's potent vasodilatory action, and include headache, flushing and dizziness. Generally, these effects are mild to moderate in severity and transient, usually diminishing with continued treatment. Thus, sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud's phenomenon. Further, promising results shown by the nifedipine GITS formulation, with its advantage of once daily administration suggest that it is likely to become one of the preferred nifedipine formulations for the treatment of hypertension and the various forms of angina.
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PMID:Sustained release nifedipine formulations. An appraisal of their current uses and prospective roles in the treatment of hypertension, ischaemic heart disease and peripheral vascular disorders. 171 8


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