Home blood pressure monitoring in general practice: expectations and concerns.
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Blood Pressure↗
Biomedical subjects
Manuel Velasco
Publications and source records attributed to Manuel Velasco.
Dopaminergic receptors: a new antihypertensive mechanism.
The neutrotransmitter dopamine, precursor of noradrenaline, induces a variety of cardiovascular and renal physiological responses, including an increase in myocardial contractility and cardiac output without changes in heart rate, passive and active vasodilatation, diuresis and natriuresis. These responses result from its interaction with the dopamine receptors D1, D2, D3, D4 and D5. In addition, recent findings suggest the existence of D6 and D7 receptors. In some types of hypertension dopamine is known to influence the control of arterial pressure by influencing the central and peripheral nervous system and target organs such as the kidneys and adrenal glands. Since dopamine and its derivatives have been shown to have antihypertensive effects, it is important to review the physiological and pharmacological aspects of dopamine and its receptors, and the clinical uses that they could have in the therapy of arterial hypertension.
Animals↗
Metoclopramide-Induced Vascular Hyperreactivity: A Comparative Study Between Normotensive and Hypertensive Subjects.
In the present study, we have evaluated the cardiovascular responses to the cold pressor test (CPT) under intravenous metoclopramide (MTC) treatment (7.5 &mgr;g kg(minus sign1) min(minus sign1)) during a 30-min period and two additional periods, before and after MTC by using 5% glucose solution. There was a vascular hyperreactivity induced by MTC, Delta mm Hg was 21.4/24/1 mm Hg (systolic/diastolic blood pressure [BP]) during MTC versus Delta 17.2/17.9 mm Hg during 5% glucose infusion. In nine hypertensive subjects, Delta mm Hg was 36.8/25.7 during MTC versus Delta 31/24 mm Hg during 5% glucose. Bromocriptine pretreatment (7.5 mg daily for 7 days) antagonized MTC-BP increase during CPT. We conclude the following: (1) MTC induces a greater BP response during CPT which is blocked by using bromocriptine, a known DA(2) dopaminergic agonist. (2) A dopaminergic influence is present during CPT in normotensive and hypertensive subjects.
Journal Article↗
Dopaminergic Influence on the Cardiovascular and Hormonal Responses to Cold Stress in Hypertensive Patients.
Immersion of one hand into ice water (cold pressor test) in eight hypertensive subjects induces elevation of mean arterial pressure, increase in heart rate, and no significant changes of plasma renin activity and plasma aldosterone concentrations. Domperidone, a DA2 dopaminergic antagonist, attenuates heart rate increase induced by the cold pressor test, and the combination of bromocriptine, a known DA2 dopaminergic agonist, with domperidone again provoked a heart rate increase during the cold pressor test. Domperidone caused an increase of both plasma renin activity and plasma aldosterone concentrations, which were reversed by bromocriptine. These results suggest that a dopamine-receptor stimulation is taking place during the cold pressor test.
Journal Article↗
Central Acting Antihypertensive Drugs: Past, Present, and Future.
The central antihypertensive drugs such as methyldopa or clonidine have been agents of importance in the therapy of hypertension. Due to the side effects and the rebound hypertensive phenomenon in the case of clonidine, the use of these agents have been clearly diminished. There are several evidences that a new type of receptor, imidazoline receptor, is present in the central nervous system and in the periphery. A specific agonist for these receptors, rilmenidine, has been studied in experimental animals and in hypertensive patients. Clinical studies have shown that rilmenidine exhibits similar efficacy but a better tolerability compared to clonidine. Rilmenidine may represent a good alternative in the therapy of hypertension.
Journal Article↗
Cardiovascular and Hormonal Effects of Domperidone, A Peripheral Dopaminergic Blocker, in Bromocriptine-Treated Hypertensive Patients.
Nine patients with mild or moderate essential hypertension were studied at the Vargas Hospital of Caracas, Venezuela. After antihypertensive treatment discontinuation, all patients were placed on placebo during a 1-week period, after which domperidone, a peripheral DA(2) dopaminergic blocker, was orally administered at the dose of 20 mg every 12 h during a period of 1 week. A final 1-week period of bromocriptine, 2.5 mg orally every 8 h, followed the domperidone period. Cold pressor test caused an increase of mean blood pressure and of heart rate, which was more accentuated after adding bromocriptine. Domperidone also caused an increase of serum aldosterone levels. Our results suggest that a dopaminergic mechanism is acting during the cold pressor test and during aldosterone secretion.
Journal Article↗
Effect of Domperidone on the Bromocriptine-Induced Antihypertensive Action in Hypertensive Patients.
Dopaminergic receptors have been involved in the cardiovascular and renin-angiotensin systems (RAS). We have recently reported that bromocriptine is an effective antihypertensive drug by stimulating DA(2) dopaminergic receptors. However, the nature of the dopaminergic receptors in RAS has not been established. Ten outpatients with essential hypertension were treated at the Vargas Hospital with bromocriptine (BR) (11.25 mg day(minus sign1)), a DA(2) dopaminergic agonist, for a 2-week period, after which an oral dose of 30 mg day(minus sign1) of domperidone (DO), a peripheric DA(2) dopaminergic antagonist, was added for 2 additional weeks. The active period was preceeded by a 2-week placebo period. Bromocriptine decreased blood pressure (BP) significantly by 19/9 mm Hg (systolic/diastolic BP). Bromocriptine did not cause heart rate (HR) changes. Bromocriptine decreased plasma aldosterone (ALD) without altering plasma renin activity (PRA). Domperidone partially blocked bromocriptine-induced antihypertensive submaximal treadmill effects and reversed ALD decrease. Exercise response was not significantly altered by BR + DO. We conclude the following: (1) BR is an effective antihypertensive agent; (2) BR seems to be acting at both the central and peripheric nervous systems, and (3) the nature of the dopaminergic receptor involved in renin secretion does not seem to be DA(2).
Journal Article↗
Role of angiotensin II AT1 receptor blockers in the treatment of arterial hypertension.
Hypertension is a very common condition and the most important risk factor for the occurrence of cardiovascular events. The hyperactivity of the renin-angiotensin-aldosterone system is considered a cardiovascular risk factor in subjects with essential hypertension. The intrinsic vascular abnormality in which the renin-angiotensin-aldosterone system is clearly the milieu for the development of the pathologic changes in blood vessel walls is one of the causes of the establishment of hypertension. Many drugs with different mechanisms of action have been used for the treatment of hypertension and its vascular complications. Nevertheless, the utilities of many drugs are limited by their adverse effects. Continuous research in the search for new pharmacological agents for the treatment of hypertension has led to the development of angiotensin II receptor type AT1 blockers. The most important functions mediated by AT1 receptors include: vasoconstriction, induction of the production and release of aldosterone, renal reabsorption of sodium, cardiac cellular growth, proliferation of vascular smooth muscle, increase of peripheral noradrenergic action and the central activity of the sympathetic nervous system, stimulation of vasopressin release, and inhibition of renin release from the kidney. The angiotensin II receptor type AT1 blockers inhibit the interaction of angiotensin II with its AT1 receptor. These agents lower blood pressure without producing cough as a side effect since, unlike the angiotensin-converting enzyme inhibitors they do not influence the levels of bradykinin or substance P. Hence, these drugs are suitable for the treatment of hypertensive patients who require therapy with a drug blocking the effect of angiotensin-converting enzyme but cannot use angiotensin-converting enzyme inhibitors due to cough as a side effect.
Angiotensin II↗
Calcium antagonists and atherosclerosis protection in hypertension.
Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.
Animals↗
Endothelium and hypertensive disorders in pregnancy.
Pregnancy-induced hypertension is one of the complications that obstetricians fear most due to its sudden appearance, its changing clinical presentation, its rapid evolution, and its association with high fetal and maternal morbidity and mortality. Because of these reasons, preeclampsia has been studied widely. But although the search for answers to many questions about its etiopathogenesis and physiopathology has led to numerous researches, after many years of studies and efforts there still exist obscure and enigmatic aspects about them. Today, various risk factors for the development of this entity have been identified, and a combination of different hypotheses has been proposed to try to find an approximation to the real solution for this problem, which could probably lead to better therapeutic management.
Endothelium, Vascular↗
Trimetazidine diminishes fasting glucose in rats with fasting hyperglycemia: a preliminary study.
Trimetazidine is a drug with cardioprotective properties used in coronary artery disease. Its effect has been attributed to the inhibition of the long chain fatty acids intramitochondrial transport via carnitine-palmitoyl-transferase-1. Clinical evidence supports the possibility that trimetazidine is able to improve the fasting glycemia in diabetic patients. For this reason, the objective of the present study was to determine the effect of trimetazidine on serum glucose of Sprague-Dawley rats with fasting hyperglycemia. All animals received water and food "ad libitum." Blood glucose was measured weekly to confirm fasting hyperglycemia in rats. The rats were treated for 1 month with trimetazidine (1 mg/kg), and blood samples were collected (in the fasting period) on the last day of treatment (the 30th day); and then on the 15th day posttreatment, measurements of plasma glucose were taken. Fasting plasma levels after 30 days of trimetazidine administration decreased significantly from 141.2 +/- 3.3 mg/dL (pre-drug) to 120.9 +/- 5.8 mg/dL (P<0.01). 15 days after the end of treatment, fasting plasma glucose levels (137.0 +/- 7.0 mg/dL) were close to the pretreatment levels but significantly different (P<0.05) from levels on day 30 of treatment. These data suggest that trimetazidine improved blood glucose utilization in rats with fasting hyperglycemia.
Animals↗
Increased serum malondialdehyde and decreased nitric oxide within 24 hours of thrombotic stroke onset.
BACKGROUND AND PURPOSE: Ischemia/reperfusion generates free oxygen radicals, which react with the unsaturated lipids of biomembranes resulting in the generation products such as malondialdehyde. Malondialdehyde could be a sensor for tissue damage and reperfusion. Nitric oxide, released due to the early arrival of leukocytes in the brain parenchyma, could be a sensor for nonflow phenomenon. Thereby, the purpose of this research was to evaluate the behavior of malondialdehyde and nitric oxide within the 24 hours after the stroke onset. METHODS: Fifteen patients up to an age of 49 years, admitted to the emergency of University Hospital and Chiquinquirá Hospital in Maracaibo, Venezuela, were examined by a neurologist and underwent 12-lead electrocardiograms and computed tomography for the diagnosis of thrombotic stroke. Serum malondialdehyde and nitric oxide were measured as thiobarbituric acid adducts and total nitrites. Data were collected within the 24 hours after the stroke onset. RESULTS: Malondialdehyde for patients with stroke had a significant increase (P<0.001) when compared with healthy controls (47.9 +/- 7.1 vs. 1.7 +/- 0.2 micromol/L). Conversely, serum nitric oxide for patients with stroke had a significant decrease (P<0.001) when compared with the control group (14.5 +/- 1.4 vs. 41.3 +/- 3.7 micromol/L). The lowest values of malondialdehyde and the highest values of nitric oxide were observed in two patients, who died. CONCLUSIONS: Serum levels of malondialdehyde increase, and serum levels of nitric oxide diminish within 24 hours after the onset of thrombotic stroke onset. This suggests that serum malondialdehyde level could be used as potentially reliable and sensitive marker for reperfusion, whereas nitric oxide levels could acts as potential biochemical sensor for nonreflow phenomenon.
Aged↗
The actions of dopamine on the airways.
BACKGROUND: Dopamine exerts inhibitory and excitatory effects on different systems. In the lungs, dopamine modulates respiratory functions through carotid bodies and modulates pulmonary blood vessel tone, alveolar liquids, and bronchial exchange, and possibly participates in the regulation of airways diameter. It has been reported that dopamine has no acute effect on human airways in normal subjects or those with asthma background. However, inhaled or infused dopamine decreased histamine-induced bronchoconstriction in both normal and asthmatic subjects. We have examined the possible modulating effect of dopamine on bronchial diameter by administering inhaled dopamine and the DA2 dopaminergic blocker metoclopramide to subjects with various degrees of bronchial tone. METHODS: We examined 56 volunteers. Arterial blood pressure and heart rate were determined in every subject. By means of spirometry, we measured forced vital capacity, forced expiratory volume in the first second, maximal forced expiratory flow, and forced expiratory flow at 50% of vital capacity, before and after each treatment. By inhalation with a nebulizer, we administered dopamine (0.5 microg/kg/min) to 10 healthy subjects, 10 subjects with asthma without acute bronchospasm, and 16 subjects with acute asthma attack; intravenous metoclopramide (7 microg/kg/min) was administered to 10 healthy subjects and 10 subjects with asthma without acute bronchospasm. For ethical reasons, metoclopramide was not used in subjects with acute asthma attack. STATISTICS: non-parametric Wilcoxon tests for paired samples, ANOVA tests, and Bonferroni multiple comparison tests were performed. RESULTS: Inhaled dopamine increased forced expiratory volume in the first second, forced vital capacity, maximal forced expiratory flow, and forced expiratory flow at 50% of vital capacity in the acute asthma attack group, but there were no modifications in the healthy group or in the asthma without acute bronchospasm group. Metoclopramide did not induce changes in respiratory parameters in healthy individuals or in those with asthma without acute bronchospasm. CONCLUSIONS: Inhaled dopamine was able to induce bronchodilatation when the bronchial tone was already increased by acute asthma attack, but it did not modify the resting bronchial tone in normals or in asthmatics without acute bronchospasm. DA2 blockade with metoclopramide did not modify resting bronchial tone either. We suggest that dopamine exerts a modulatory effect on bronchial tone of human airways depending on the degree of existing basal tone.
Administration, Inhalation↗