Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and obesity are closely related. Obese patients tend to have increased intravascular volume and cardiac output and decreased total peripheral vascular resistance and plasma renin activity. Lean patients with essential hypertension usually have increased total peripheral resistance. Left ventricular adaptation in obesity consists of eccentric left ventricular hypertrophy (LVH), regardless of the level of arterial pressure. Obesity and hypertension occurring together place a dual burden on the left ventricle and are associated with systolic and diastolic dysfunction, lipid abnormalities, insulin resistance, and a propensity for frequent, complex ventricular arrhythmias. Congestive heart failure and sudden death are common sequelae of obesity-hypertension and LVH. Treatment should include vigorous efforts at weight reduction and sodium restriction. Diuretics are ideal agents from a hemodynamic standpoint but often do not improve the total risk profile, with the possible exception of indapamide (Lozol). Calcium blockers may be ideal agents because of their favorable effects on both hemodynamics and total cardiovascular risk profile.
 ...
PMID:Left ventricular hypertrophy. Its relationship to obesity and hypertension. 153 69

Amlodipine and nitrendipine are calcium antagonists of the 1,4-dihydropyridine group which differ in their pharmacokinetic and pharmacodynamic properties. The clinical relevance of these differences was investigated in a study designed to compare the efficacy and safety of once-daily amlodipine (5 mg) and nitrendipine (20 mg) in patients with mild-to-moderate essential hypertension. Ambulatory blood pressure monitoring and conventional measurements showed that amlodipine and nitrendipine produced comparable reductions in blood pressure after 4 weeks of treatment. However, the onset of the antihypertensive effect was gradual for amlodipine, while most of the reduction achieved at the end of treatment with nitrendipine was seen after the first dose. There were no significant changes in heart rate with amlodipine, but significant increases occurred during the first 6 h of nitrendipine treatment. Amlodipine was associated with a significantly lower incidence of vasodilator-related adverse effects at initiation of therapy (headache, flushing, tachycardia) compared with nitrendipine, which may reflect its slower onset of action. The different pharmacodynamic and toleration profiles of amlodipine and nitrendipine at therapeutically equivalent doses suggest that amlodipine may have advantages in the treatment of hypertension, especially in terms of the low incidence of acute side effects, which may ultimately translate into improved patient compliance.
 ...
PMID:Amlodipine compared to nitrendipine in hypertensive patients: the effects on toleration in relationship to the onset of action. 153 15

We investigated in six patients with essential hypertension the effect of a low dose atrial natriuretic factor infusion for 5 days on the diurnal rhythm of renal electrolyte excretion. Atrial natriuretic factor infusion increased the net excretion of sodium and caused a delay in its time of maximal diurnal urinary excretion. Similarly, atrial natriuretic factor caused an increase in the net excretion of chloride, calcium, and magnesium and also changed the diurnal rhythms of these electrolytes. In contrast, atrial natriuretic factor did not change the net excretion of potassium, phosphate, and uric acid, nor did atrial natriuretic factor change the diurnal rhythms of these solutes. During baseline, the time points of maximal urinary excretion of sodium and potassium overlapped, whereas atrial natriuretic factor infusion caused sodium excretion to peak 2.2 +/- 0.3 hours (p less than 0.02) after the potassium excretion peak. During baseline, the time of maximal urinary excretion of sodium did not correlate with the time of highest blood pressure, whereas it correlated negatively with mean plasma aldosterone concentration. In contrast, during atrial natriuretic factor infusion the time of maximal urinary excretion of sodium correlated positively with the time of highest blood pressure, whereas it did not correlate with mean plasma aldosterone concentration. These data suggest that atrial natriuretic factor is involved with the diurnal rhythm of the urinary excretion of sodium and that atrial natriuretic factor-induced natriuresis is mediated in part by blood pressure and plasma aldosterone.
 ...
PMID:Atrial natriuretic factor influences renal diurnal rhythm in essential hypertension. 153 13

The group of calcium channel blockers includes drugs with marked structural differences and hence different fundamental pharmacodynamic and pharmacokinetic properties. The combination of these properties characterizes the different hemodynamic and electrophysiological effects of individual calcium antagonists as well as their profile of adverse effects. In treatment of essential hypertension the most important criteria for choosing one of the calcium antagonists are the rate of adverse effects, which is different between individual drugs of this class, and the possibility of once-daily administration to improve compliance. The effect on blood pressure in contrast is comparable for all calcium antagonists. In ischemic heart disease with markedly reduced left-ventricular function verapamil, diltiazem, but also nifedipine should be avoided as these drugs have important negative inotropic effects which may induce congestive heart failure and adversely affect prognosis. For monotherapy in this indication verapamil and diltiazem are drugs of first choice in patients with normal left-ventricular function, whereas second generation calcium antagonists of the dihydropyridine class can be given also in patients with reduced left-ventricular function and in combination with beta-blockers. Dihydropyridine derivatives with reflectory increase of sympathetic tone, such as nifedipine, should be administered in combination with beta-blockers only. Whereas calcium antagonists are first-line drugs for antihypertensive and anti-ischemic treatment, results in secondary prevention after myocardial infarction are rather disappointing when compared with established alternatives.
 ...
PMID:[Are all calcium antagonists alike?]. 153 50

To evaluate the role of regional hemodynamics in the anti-hypertensive effect of mepirodipine, a new dihydropyridine-derivative calcium antagonist, we measured systemic, renal, hepatic, and forearm hemodynamics in 10 patients with essential hypertension treated with mepirodipine (15 mg/day) for 4 weeks. After the administration of mepirodipine, a significant decline in mean blood pressure (-13.8 +/- 2.3%, p less than 0.01) accompanied by a decrease in systemic vascular resistance (-21.1 +/- 2.6%, p less than 0.01) was observed. Although forearm vascular resistance did not change significantly, both renal (-19.2 +/- 6.7%, p less than 0.01) and hepatic vascular resistance (-17.6 +/- 3.8%, p less than 0.01) decreased considerably. The decrements of mean blood pressure with mepirodipine did not correlate with those of hepatic or forearm vascular resistance but correlated positively with those of renal vascular resistance (r = 0.699, p less than 0.05). Moreover, the increment of renal blood flow with mepirodipine was negatively correlated with the pretreatment level of renal blood flow (r = -0.670, p less than 0.05); renal blood flow increased to a greater extent in patients with lower pretreatment renal blood flow. These findings suggest that the oral administration of mepirodipine in patients with essential hypertension can produce selective vasodilation in the renal vasculature, which may play an important role in the relatively long-term antihypertensive effect of this drug.
 ...
PMID:The role of renal hemodynamics in the antihypertensive action of mepirodipine, a new calcium antagonist. 153 73

Platelet intracellular free calcium concentration [Ca2+]i from patients with essential hypertension has been found to be elevated, but the intracellular effects of this increase are still unclear. As protein phosphorylation is an important regulatory step in cell activation and increased protein phosphorylation has been demonstrated in platelets from hypertensive animals, we investigated protein phosphorylation and [Ca2+]i in platelets from patients with essential hypertension and age-matched normotensives. We measured the 32P incorporation into a 20 kDa protein and a 47 kDa protein in 17 hypertensive patients and 20 normotensive, age-matched subjects. The [Ca2+]i was measured with the fluorescent dye fura-2. Protein phosphorylation and [Ca2+]i were assessed in unstimulated platelets and after exposure of the cells to 0.1 and 0.25 U/mL thrombin at 20, 60, and 300 sec. In addition we assessed the activity of protein kinase C by incubating the platelets with phorbol-ester TPA at 20, 60, and 300 sec. Basal phosphorylation of the two proteins was not different between the two groups. After exposure of the platelets to thrombin 32P, incorporation into the 20 kDa protein and the 47 kDa protein was significantly increased in platelets from hypertensive patients at all times. Furthermore, the specific stimulation of protein kinase C with TPA resulted in a significantly higher phosphorylation of the 47 kDa protein, whereas the 20 kDa protein was not phosphorylated after incubation with TPA for 1 min. Basal [Ca2+]i was higher in platelets from hypertensive patients (124 +/- 7 nmol/L v 104 +/- 5 nmol/L, P less than .05), although there was a wide overlap between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protein phosphorylation and intracellular free calcium in platelets of patients with essential hypertension. 157 40

The effects of the calcium antagonist nicardipine on the pressor response to mental arithmetic, cold pressor and exercise tests have been studied in fifteen patients with established mild to moderate essential hypertension. Nicardipine 20 mg p.o. showed a hypotensive effect within 60 min, associated with a fall in total peripheral resistance and an increase in heart rate. As the pressor response to each stress was not affected by nicardipine, the peak blood pressure reached during each stress was lower. Nicardipine lowers blood pressure at rest as a result of arteriolar dilatation, associated with reflex tachycardia. The pressor responsiveness to various stresses was not affected by nicardipine.
 ...
PMID:Effect of nicardipine on haemodynamic response to stress in hypertension. 157 44

To investigate the role of cytosolic free calcium, [Ca2+]i, in secondary hypertension, the levels in platelets from 14 secondary hypertensives (7 renovascular hypertension, 7 primary aldosteronism) were compared with those from 21 essential hypertensives and 15 normotensives by means of the fluorescent indicator, quin-2. The mean BP was significantly higher in both the secondary hypertensives and essential hypertensives (122 +/- 8 and 124 +/- 12 mmHg) than in the normotensives (89 +/- 10 mmHg). Cytosolic free calcium in platelets was significantly higher in the essential hypertensives, but not in the secondary hypertensives, compared with the normotensives (182 +/- 34, 141 +/- 17, 138 +/- 15 nM respectively). There was no significant difference in platelet [Ca2+]i between renovascular hypertension and aldosteronism (142 +/- 19 versus 139 +/- 16 nM). There was no correlation between platelet [Ca2+]i and plasma renin activity, plasma aldosterone concentration or plasma noradrenaline concentration in the three groups. Thus, the increase in platelet [Ca2+]i seen in essential hypertension was not found in patients with secondary hypertension. Our results suggest that the cytosolic calcium handling of secondary hypertensive patients with renal artery stenosis or primary aldosteronism differs from that of essential hypertensives.
 ...
PMID:Cytosolic free calcium concentration in platelets in patients with renovascular hypertension and primary aldosteronism. 158 34

The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t 1/2 beta) and may be suitable for twice-daily administration. Amlodipine is an exception with a t 1/2 beta in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced first-pass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs.
 ...
PMID:Clinical pharmacokinetics of calcium antagonists. An update. 158 55

To characterize the long-term effects of calcium antagonists on renal function in hypertension felodipine was used to treat 14 patients with severe uncontrolled hypertension associated with renal functional impairment: six patients had renal parenchymal hypertension, six had essential hypertension and two had renovascular hypertension. Mean blood pressure was 197 +/- 2/115 +/- 3 mm Hg despite treatment with three or more antihypertensive drugs. Mean glomerular filtration rate (GFR) was 39 +/- 6 ml/min (Cr-EDTA clearance) before initiation of felodipine treatment. All patients experienced a blood pressure reduction after starting felodipine treatment, which persisted during long-term therapy in combination with previous medication except former vasodilating drugs. Blood pressure after 12 and 24 months was 152 +/- 7/89 +/- 2 and 157 +/- 5/90 +/- 2 mm Hg, respectively. Patients with moderately impaired GFR and absence of progressive renal disease (N = 8) manifested an increase in GFR after 6 and 12 months on felodipine (59 +/- 10 to 63 +/- 7 and 70 +/- 6 ml/min, respectively, P less than 0.05). Renal plasma flow (PAH clearance) exhibited only a slight increase (315 +/- 68 to 340 +/- 63 and 314 +/- 69 ml/min) with a consequent increase in filtration fraction (18 +/- 1 to 21 +/- 1 and 20 +/- 1%, NS). At follow-up after six to eight years patients with initial GFR greater than or equal to 50 ml/min had a maintained renal function. In five patients a progressive deterioration of renal function had been documented.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Long-term effects of felodipine in patients with reduced renal function. 161 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>