Dopamine versus norepinephrine: is one better?

Dopamine and norepinephrine are widely used as first line agents to correct hypotension in patients with acute circulatory failure. There has been considerable debate in recent years as to whether one is better than the other. Both drugs can increase blood pressure in shock states, although norepinephrine is more powerful. Dopamine can increase cardiac output more than norepinephrine, and in addition to the increase in global blood flow, has the potential advantage of increasing renal and hepatosplanchnic blood flow. However, dopamine has potentially detrimental effects on the release of pituitary hormones and especially prolactin, although the clinical relevance of these effects is unclear. Observational studies have provided conflicting results regarding the effects of these two drugs on outcomes, and results from a recently completed randomized controlled trial are eagerly waited.

Prolonged antihypertensive effect of amlodipine: a prospective double-blind randomized study.

Amlodipine is a calcium antagonist with a long elimination half-life (35 to 50 h) allowing a once daily dosing in the treatment of hypertension. This randomized, double-blind study was performed to assess the residual antihypertensive effect of amlodipine 5 mg O.D. 3 days after discontinuing therapy in previously well-controlled mild to moderate hypertensive patients. Blood pressure (BP) was evaluated by conventional (OBP) and by ambulatory blood pressure monitoring (ABPM). Amlodipine 5 mg OD administered during a 6-week period, significantly reduced both OBP and ABPM mean values (p < 0.05), whereas no change in heart rate was observed. At the end of the active treatment period, adequately controlled patients were randomized either to amlodipine 5 mg OD (group A) or amlodipine for 12 days followed by a 3-day period on placebo. After this double-blind treatment phase, group P exhibited no significant increase in BP (assessed by OBP or ABPM) when compared to group A. In conclusion, the duration of action of amlodipine extends largely beyond the 24-h span, and when patients omit their treatment for 3 days BP does not significantly increase.

Diurnal variations in cardiovascular function and glucose regulation in normotensive humans.

To define the physiological relationships between cardiovascular function, glucose regulation, and insulin secretion, we submitted nine young normotensive subjects to ambulatory blood pressure monitoring and blood sampling at 20-minute intervals for 24 hours to measure glucose, insulin, C peptide, cortisol, and growth hormone. Subjects ingested three identical carbohydrate-rich meals in the morning (8:30 AM), early afternoon (2 PM), and evening (8 PM). On the following day, they underwent an intravenous glucose tolerance test for quantification of insulin sensitivity. Significant postmeal increases in systolic pressure averaging 18 +/- 10 mm Hg in the morning, 18 +/- 8 mm Hg in the early afternoon, and 26 +/- 19 mm Hg in the evening were observed. Postprandial variations in diastolic pressure and heart rate were significant only for the morning meal. The magnitude of the postprandial increases in systolic pressure was correlated with the amount of insulin secreted in the morning but not later in the day. Pulses of growth hormone consistently occurred 3 to 4 hours after the morning and midday meals, as well as after the onset of sleep. Our findings indicate that under normal conditions, there is a quantitative relationship between postprandial insulin secretion and blood pressure.

Cardiorespiratory transfer during sleep: a study in healthy young men.

This study tested the concept that changes in breathing parameters account for modifications in respiratory-related blood pressure (BP) and R-R interval (RRI) variability during nocturnal sleep. BP (Finapres), electrocardiogram, respiration (Respitrace), and polygraphic sleep recordings were recorded continuously in 13 healthy men aged 18-37 yr. The transfer characteristics identified by coherence and gain measures between the calibrated thoraco-abdominal motion and the respiratory-related BP and RRI variability evidenced a consistent increase during transitions from wake to light sleep and from light to deep sleep but returned to waking levels during rapid-eye-movement sleep (P < 0.0001). These changes were related to the specific modifications occurring in the respiratory rate, tidal volume, and ribcage-to-abdominal motion ratio during the different sleep stages (0.28 < r < 0.39; P < 0.0001). This study demonstrates 1) that modifications in the breathing pattern account for 8-15% of the variance in the cardiorespiratory transfer, and 2) that respiratory modulation of vagal activity is not the main mechanism controlling the magnitude of the respiratory-related BP and RRI variability during sleep.

Effects of wake and sleep stages on the 24-h autonomic control of blood pressure and heart rate in recumbent men.

Fifteen recumbent young health volunteers underwent 24-h beat-to-beat blood pressure (BP) and interbeat interval (IBI) recordings to explore the effects of wake and polygraphically recorded sleep on the nyctohemeral variations in the spectral frequency components of BP and IBI and in the arterial baroreflex sensitivity (BRS), independent of the confounding effects of changes in posture and physical activity. Spectral analysis of BP and IBI provided markers of sympathetic and vagal controls and of arterial BRS. When falling asleep, the low-frequency (LF) BP and IBI components showed a marked decrease while there was a clear-cut increase in the high-frequency (HF) IBI component. In contrast, only a slight nighttime rapid eye movement-related arterial BRS increase was observed. The final morning awakening induced a pronounced decrease in arterial BRS and the HF IBI component while there was a marked rise in the LF BP component. Hence, a clear 24-h variation in sympathetic and vagal tone but not in arterial BRS persists, independent of changes in activity and position.

Carvedilol in the treatment of mild to moderate hypertension: experience with ambulatory blood pressure monitoring.

An open randomized study was conducted in mild to moderate hypertensive patients to evaluate, over a 3 months treatment period, the efficacy and tolerability of carvedilol 25 mg OD and to compare, in case of insufficient results with 25 mg, the efficacy and tolerance of carvedilol 50 mg and carvedilol 25 mg coadministered with diuretics. Mean office blood pressure (sitting) of the 91 patients who completed the study according to the protocol was reduced from 161/100 to 147/91 mm Hg after 4 weeks of treatment carvedilol 25 mg OD. Continuation of carvedilol 25 mg produced no further reduction in blood pressure. Increasing carvedilol to 50 mg OD or addition of diuretics further reduced blood pressure. Ambulatory blood pressure measurements showed a significant reduction in both SBP and DBP after 3 months treatment in the three groups, as well as with respect to the circadian profile of blood pressure and heart rate. Large differences between ambulatory and office blood pressure were observed: 37% of the patients diagnosed as mild to moderate hypertensives according to office blood pressure before treatment had mean daytime DBP < 90 mm Hg and 39% mean daytime SBP < 140 mm Hg. Twenty-eight percent of the patients experienced adverse events; they occurred mainly at the beginning of treatment; less than 5% of participants withdrew due to adverse events. The most frequent adverse events were fatigue, vertigo and asthenia. This study showed that carvedilol is safe and effective in the treatment of mild to moderate hypertension and that there is a high prevalence (nearly 40%) of low ambulatory blood pressure means in a population labelled as mild to moderate hypertensive.