Mario Blanco

The cold pressor test: pharmacological and therapeutic aspects.

In this review article we discuss several aspects of the physiology, diagnosis, and pharmacology of the cold pressor test. The cold pressor test has been used for the diagnosis of cardiovascular reactivity in normotensive and hypertensive subjects. Some authors have stated that the cold pressor test will identify normotensive candidates at future risk of suffering from hypertensive disease. Interestingly, not all antihypertensive drugs block the exaggerated pressor response induced by cold stress. The most beneficial compounds belong to the α- and β-blocker groups. Furthermore, several neurohormones such as norepinephrine, endothelins, prostaglandins, and angiotensin II have been reported to be released during cold exposure. The neurophysiology of cold pressor test indicates that after stress a great sympathetic discharge is induced at the spinal cord and terminal endings of the sympathetic nervous system. The release of norepinephrine is the cause of arteriolar vasoconstriction and elevation of blood pressure.

Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine

90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.

Metoclopramide enhances labetalol-induced antihypertensive effect during handgrip in hypertensive patients.

The effects of metoclopramide, labetalol, and metoclopramide plus labetalol treatments on baseline cardiovascular parameters and isometric handgrip-induced changes were evaluated in 11 hypertensive subjects. Although all treatments were effective in reducing resting systolic (SBP) and diastolic (DBP) blood pressures, the combination of metoclopramide and labetalol appeared to provide a greater decrease (changes in SBP/DBP: 15/11 mm Hg, P < 0.05; from 149 ± 4/95 ± 4 mm Hg to 134 ± 5/84 ± 3 mm Hg) than did labetalol alone (changes in SBP/DBP: 10/9 mm Hg, P < 0.05; from 149 ± 4/95 ± 4 to 139 ± 4/86 ± 3 mm Hg). At 2 minutes, handgrip increased blood pressure on placebo (changes in SBP/DBP: 34/7 mm Hg, P < 0.001). In the presence of metoclopramide and metoclopramide plus labetalol, however, handgrip induced lesser increases in blood pressure (changes in SBP/DBP: 23/7 mm Hg, P < 0.01, and 18/4 mm Hg, P < 0.01, for metoclopramide and metoclopramide plus labetalol treatments). We conclude that (1) metoclopramide lowers blood pressure in hypertensive patients; (2) metoclopramide attenuates blood pressure response to isometric handgrip; and (3) both compounds, labetalol and metoclopramide, seem to have a pharmacologic interaction concerning blood pressure decrease. A clinical significance is suggested for the metoclopramide effect.

Dopaminergic influence on cardiovascular responses to exercise stress in hypertensive subjects.

Ten hypertensive subjects were studied at the Vargas Medical School in Caracas, Venezuela. They were submitted to submaximal treadmill exercises according to Bruces protocol under treatment with dopaminergic drugs (metoclopramide, bromocriptine). Before and during submaximal exercises, metoclopramide caused a hypotensive effect accompanied by an increased heart rate, which was blocked by the administration of bromocriptine. We conclude that a probable dopaminergic modulatory influence takes place during exercise.

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 μg kg-1 min-1) 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, mm Hg was 21.4/24.1 mm Hg (systolic/diastolic blood pressure [BP]) during MTC versus ± 17.2/17.9 mm Hg during 5% glucose infusion. In nine hypertensive subjects, ± mm Hg was 36.8/25.7 during MTC versus ± 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 DA2 dopaminergic agonist. (2) A dopaminergic influence is present during CPT in normotensive and hypertensive subjects.

Attenuated metoclopramide-induced vascular hyperreactivity to cold stress in athletic subjects.

We have previously reported a metoclopramide-induced vascular hyperreactivity to the cold pressor test (CPT) in normotensive and hypertensive subjects. The present study was designed to determine whether the state of physical training influences the cardiovascular responses to the CPT in normotensive subjects under metoclopramide (MTC) treatment. In 20 untrained subjects and 32 athletes (football players and runners), the blood pressure and heart rate responses to the CPT were studied after a 30-minute infusion of MTC (7.5 μg/kg per minute) and two placebo periods, before and after MTC, with 5% glucose solution. Under placebo conditions, the CPT produced significant increases of systolic blood pressure (SBP) in the untrained subjects and the runners, but not in the football players (17.2, 17.8, and 6.5 mm Hg for untrained subjects, runners, and football players, respectively). The runners responded with a lesser increase in diastolic blood pressure (DBP) during the CPT than did the others (15.8,17.9, and 18.2 mm Hg for runners, untrained subjects, and football players, respectively). In the presence of MTC, the CPT induced a larger increase in blood pressure (SBP/DBP) in the untrained subjects (21.4/24.1 mm Hg) than in the football players (10/18.7 mm Hg) and runners (18.7/13.9 mm Hg). MTC diminished the hyperreactivity responses to the CPT in the trained subjects (41 and 56% for football players and runners, respectively). Our conclusions are as follows: (1) Vascular responses to cold stress are attenuated in athletic subjects compared with untrained subjects. (2) The metoclopramide-induced vascular hyperreactivity, formerly reported for normotensive and hypertensive subjects, seems to be absent in trained subjects. (3) It is suggested that a probable dopaminergic system adaptation occurs during exercise.

GENDER-RELATED CARDIOVASCULAR RESPONSES TO COLD PRESSOR TEST IN NORMOTENSIVE SUBJECTS

We have studied 20 normotensive subjects under metolopramide (MTC) treatment. MTC was administered by intravenous infusion during a 30-min period at the dose of 7.5 μg kg 1 min-1. Two 5% glucose infusion 30-min periods, before and after MTC, were used. Subjects were asked to immerse their right hands in ice water (0–4°C) for 60 s during each protocol period. Blood pressure was decreased by MTC before the cold pressor test (CPT). During the MTC period, there was a higher pressor response to cold stress, which was only significant for female subjects. Our results suggest that gender-dependent MTC-induced vascular hyperreactivity attributed to a dopaminergic mechanism is probably related to estrogen, progesterone, or other active metabolic breakdown products or possibly an undescribed humoral influence.