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

Labetalol, a new antihypertensive drug which combines alpha- and beta-blocking properties, was used in an open clinical trial in a mixed group of 47 adult patients with mainly essential hypertension, many of whom had been poorly controlled on other drugs. Labetalol lowered lying and standing blood pressures significantly when given alone or when combined with other antihypertensive drugs and it was generally well tolerated. It is easy to use, and in some severe cases has been dramatically effective. Mean daily dose was 767 mg. A postural hypotensive effect was seen especially in patients taking concomitant diuretics but was not troublesome. Labetalol reduced heart rate in patients who were not on previous or concomitant beta-blocker therapy. Side effects were few and did not cause major problems. A transiently or persistently weakly positive ANF was noted in nine patients; the significance of this is uncertain at this stage and needs further assessment. Raynaud's phenomenon, which had complicated previous beta-blocker therapy in some patients, improved with labetalol.
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PMID:Treatment of hypertension with labetalol. 30 82

In a double-blind, randomized, placebo-controlled study, the authors investigated the effects of different beta-adrenoceptor blocking drugs on the peripheral circulation. A single intravenous injection of the nonselective beta-blocker propranolol (0.20 mg/kg), the beta 1-selective adrenoceptor blocker metoprolol (0.25 mg/kg), and the nonselective beta-blocker with partial agonistic activity (PAA) pindolol (0.04 mg/kg) and of placebo (saline) was given to eight patients with a primary Raynaud's phenomenon and to nine untreated patients with primary hypertension. The authors measured finger skin temperature (FST), and laser Doppler estimated finger skin blood flux (LDF) before, during, and after a standardized finger cooling test, performed 25 minutes after the administration of the drugs. In both patients groups propranolol, metoprolol, and pindolol had no significant effect on FST and LDF in the first 25 minutes after administration both in comparison to baseline value and to placebo. Also, no significant differences were found in the recoveries of FST and LDF after cold challenge between all drugs and placebo in both groups. The authors conclude that no adverse effect of any type of beta-adrenoceptor blocker in comparison to placebo could be detected after a single administration on both the baseline finger skin perfusion and the recovery after cold-induced vasoconstriction. In addition, the authors could not demonstrate a favorable effect of beta 1-selectivity or PAA in comparison to a nonselective beta-adrenoceptor blocker without PAA, in any group.
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PMID:The influence of different beta-blocking drugs on the peripheral circulation in Raynaud's phenomenon and in hypertension. 135 6

The reduction of transmembranous calcium influx into vascular smooth muscle cells by calcium antagonists leads to a reduction of tension development and vascular tone. Nifedipine reduces forearm vascular resistance dose-dependently when infused into the brachial artery in patients with essential hypertension, attesting to its potent arterial vasodilator effects. This effect can be successfully utilized for the treatment of essential hypertension, where nifedipine acts by reducing increased peripheral vascular resistance, thereby normalizing the main hemodynamic derangement of hypertensive patients. In contrast to other direct-acting vasodilators, the antihypertensive effect is not accompanied by sympathetic reflex activation or volume retention, making it feasible to use nifedipine as monotherapy for hypertensive patients. Although the pathophysiologic disturbances leading to vasospasm are not clear, blockade of slow calcium channels is also effective for the treatment of Raynaud's phenomenon, reducing attack frequency, digital pain, and functional disability in many patients, particularly those with primary Raynaud's phenomenon.
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PMID:Use of nifedipine in hypertension and Raynaud's phenomenon. 207 3

Ketanserin is a 5-HT2 receptor antagonist without partial agonist properties which also possesses weak alpha 1-adrenoceptor antagonistic activity, which may explain its antihypertensive mechanism of action in patients with essential hypertension. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. The antihypertensive effect of oral ketanserin 40 mg twice daily is comparable with that of total daily doses of metoprolol 200 mg, propranolol 160 mg, captopril 100 mg, enalapril 20 mg, hydrochlorothiazide 50 mg, or alpha-methyldopa 1000 mg and is achieved without adverse effect on plasma lipoproteins or carbohydrate metabolism in patients with concomitant diabetes mellitus. Evidence from prospective studies suggests a greater antihypertensive efficacy in the elderly than in younger patients. In patients with intermittent claudication, results have been inconsistent in small studies, while a large study showed no improvement in pain-free walking distance but fewer amputations compared to placebo. In Raynaud's phenomenon symptomatic improvement relative to placebo was achieved in larger trials. Its role in preventing atherosclerotic complications requires further investigation. Ketanserin is reasonably well tolerated, the frequency of adverse effects being comparable with that of other antihypertensive drugs in controlled trials. Dizziness, tiredness, oedema, dry mouth and weight gain are the most commonly reported effects. Ketanserin prolongs QT interval in a dose-related manner, and when given in certain predisposing circumstances ventricular arrhythmias and syncope may occur. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload. Although the arrhythmogenic potential of ketanserin in patients receiving potassium-depleting diuretics requires suitable precautions, it appears that its antihypertensive activity is suited to the elderly provided plasma potassium concentrations are normal at the start of treatment and are maintained within the normal range.
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PMID:Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. 207 1

The effects of serotonin and its pharmacological antagonists on the physical flow properties of the blood have been studied far less than their effects on blood vessels, although they may be equally important. Indirect evidence suggests that in pathological circumstances serotonin may locally increase whole blood viscosity, particularly at low shear rates, decrease red cell deformability and increase the adhesiveness of white cells. Although the viscosity of the plasma alone is not affected, the rheological effects of serotonin on blood cells is probably dependent on the presence of platelets. These mechanisms may have a systemic effect in some forms of hypertension as well as in situations of local ischaemia such as Raynaud's phenomenon, atherosclerotic pregangrene of the leg or acute myocardial infarction. Specific serotonergic-antagonists, administered either orally or intravenously, normalize the increased whole blood viscosity and decreased blood filterability found in essential hypertension, following myocardial infarction and in severe leg ischaemia. The effect on red cell deformability is usually greatest when the cells are resuspended in platelet rich plasma. Ketanserin given intravenously for seven days to patients with very severe leg ischaemia, significantly improves whole blood viscosity, increases red cell transit time and most dramatically decreases pore clogging. This last effect was at least partly due to a change in the physical properties, but not the number of the white cells. The reported beneficial clinical effects of such an antagonist in various forms of peripheral ischaemia and essential hypertension may well be due, at least partly, to the normalization of the rheological properties of the blood.
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PMID:Serotonin and the flow properties of blood. 241 54

The present article deals with the pathophysiological role of serotonin in cardiovascular disease and in other disorders that are accompanied by cardiovascular pathophysiological events. The distribution of serotonin over various organs and tissues and the presence of several types of 5-HT receptors would suggest a rather important physiological role of serotonin. However, a modest serotonergic role could only be shown for the microcirculation and for the regional circulation of the brain and the intestinal wall. An important pathological role of serotonin in the carcinoid syndrome, in migraine, and in peripheral vascular disease is beyond debate, although many details remain to be established. The possibility that serotonergic mechanisms contribute to Raynaud's phenomenon and other vasospastic disorders is the subject of present discussions, although firm evidence for this view is not widely available. An involvement of peripheral serotonin in the genesis and maintenance of essential hypertension seems very unlikely, although vascular damage due to hypertension is probably enhanced by serotonin released from aggregating platelets. This ancillary process is, in particular, to be anticipated in older patients, with vascular walls predamaged by atherosclerosis. For this reason, pharmacological blockade of 5-HT2 receptors may be of potential therapeutic benefit in this category of patient. Finally, the involvement of central serotonergic mechanisms in hypertensive disease cannot be ruled out.
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PMID:Pathophysiological relevance of serotonin. 244 63

It remains to be established whether ketanserin's antihypertensive effect is caused by S2-serotonergic blockade, by alpha 1-adrenergic blockade, or by a combination of both. Ketanserin, 10 mg i.v. or 40 mg t.i.d. orally, blocked the serotonin-induced contractions of hand veins in patients with essential hypertension. Intravenous ketanserin had no effect on the venoconstrictor action of noradrenaline. The increase in digital blood flow after i.v. ketanserin, as measured by the change in digital skin temperature in patients with Raynaud's phenomenon, was not blocked by phentolamine or pretreatment with prazosin. Intravenous ketanserin also lowered arterial pressure in patients with autonomic insufficiency who were unresponsive to phentolamine. These observations suggest that alpha-adrenergic blockade is not the sole mechanism of ketanserin's cardiovascular actions in humans.
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PMID:Role of alpha-adrenergic blockade in the cardiovascular actions of ketanserin: studies in patients with essential hypertension, autonomic insufficiency, and Raynaud's phenomenon. 244 64

It remains to be established whether ketanserin's antihypertensive effect is caused by blockade of serotonergic type 2 receptors (S2), by blockade of alpha 1-adrenoceptors or by combined effect on both receptors. We therefore performed several clinical studies. Ketanserin, 10 mg i.v., lowered blood pressure in 6 patients with essential hypertension and blocked, at the same time, the contraction of hand veins to exogenous serotonin. In contrast, ketanserin had no effect on the venoconstrictor action of noradrenaline. Ketanserin also did not alter the pressor effect of bolus injections of the alpha 1-agonist phenylephrine. Furthermore, ketanserin had a distinct hypotensive effect in 4 normotensive patients with autonomic insufficiency who were unresponsive to alpha 1-adrenoceptor blockade. Moreover, the ketanserin-induced marked increase in digital blood flow in 7 patients with Raynaud's phenomenon was not blocked by pretreatment with high doses of the alpha 1-adrenoceptor blockade. However, in patients with essential hypertension, the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin. This may be related to S2 blockade of the alleged amplifying effect of serotonin on alpha 1-adrenoceptor mediated vasoconstriction but the data do not exclude concomitant alpha-blockade by ketanserin. We conclude that the mechanism of ketanserin's antihypertensive effect requires further clarification; nevertheless the data cited above do not support the view that ketanserin is nothing more than another alpha-blocker.
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PMID:Mechanism of action of ketanserin in hypertension and vasospastic disease. 282 6

Since enhanced sensitivity to verapamil in essential hypertension has been noted, a relationship between verapamil and the sympathetic nervous system has been suggested. It has also been noted that both verapamil and lumbar sympathectomy appear to decrease the vasospasm seen in Raynaud's phenomenon. To further investigate the possible interrelationship between verapamil and the sympathetic nervous system, a unilateral lumbar sympathectomy was performed on eight dogs. Two weeks later the femoral artery blood flow response to intra-arterial verapamil was compared on the sympathectomy limb side and the non-sympathectomy limb side. Blood flow measurements were done without surgical trauma by video dilution technique. Although baseline femoral artery blood flow was unchanged and equal on both sides following sympathectomy (4.6% of cardiac output), there was a significant rise, p less than 0.05, in the blood flow response to verapamil on the side of sympathectomy. Therefore, sympathectomy appears to enhance the calcium channel blocking properties of verapamil.
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PMID:Vasoactivity of verapamil in the canine hindlimb and sympathetic nervous system interaction. 296 Mar 64

Alpha methyltyrosine (alpha-MPT) was administered to 52 patients from 4 days to 10 months; 22 patients were cases of pheochromocytoma and 20 had essential hypertension. Inhibition of catecholamine synthesis in the range of 50-80% was achieved with divided daily drug dosage of from 1.0 to 4.0 g. Striking clinical benefit was noted in patients with pheochromocytoma in whom the drug was used in preparation for surgery and during chronic medical management. The drug appeared to have limited usefulness when used in essential hypertension, unless added to existing therapy with conventional agents. No beneficial effects were noted in thyrotoxicosis, glaucoma, and Raynaud's phenomenon. Untoward effects in order of decreasing incidence were: sedation (with insomnia on withdrawal), anxiety, tremor, diarrhea, and galactorrhea. Drug crystalluria, which has been observed in animals and is currently restrictive of clinical trials, was not observed in these studies. Evidence is presented that the minor conversion of alpha-MPT to methyldopa probably does not contribute significantly to the central and peripheral effects of the drug.
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PMID:Biochemical and pharmacologic effects of alpha-methyltyrosine in man. 563 45


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