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Blood pressure profile and variability in hypertensives treated with L-arginine infusion
Czarnecka1, Malczewska-Malec, Dembinska-Kiec
1Cardiac Department, Jagiellonian University School of Medicine, Kraków, Poland.
Insights
Infusing L-arginine, the precursor to nitric oxide (NO), lowered blood pressure in hypertensive men. This effect was temporary, primarily during infusion, and reduced blood pressure variability.
Area of Science:
- Cardiovascular Physiology
- Nitric Oxide Biology
Background:
- The precise role of nitric oxide (NO) in regulating systemic blood pressure in both normotensive and hypertensive individuals remains incompletely understood.
- Investigating NO's influence is crucial for developing novel antihypertensive strategies.
Purpose of the Study:
- To evaluate the impact of L-arginine, a substrate for NO synthesis, on blood pressure regulation in men with inadequately controlled primary arterial hypertension.
- To explore the potential of L-arginine as a therapeutic agent for hypertension.
Main Methods:
- A randomized controlled study involving 30 hypertensive men receiving standard antihypertensive medication.
- Intravenous administration of L-arginine or a saline placebo over 180 minutes for four consecutive days.
- Continuous monitoring of blood pressure and heart rate, alongside 24-hour ambulatory blood pressure monitoring.
- Measurement of cyclic GMP levels and urinary nitrite/nitrate concentrations as indicators of NO generation.
Main Results:
- L-arginine infusion led to significant reductions in both systolic and diastolic blood pressure (P < 0.0001) and a concurrent increase in heart rate (P < 0.001).
- The most pronounced hypotensive effect was observed on the first day of L-arginine infusion, with subsequent infusions showing a progressively smaller, yet significant, reduction.
- Ambulatory blood pressure monitoring confirmed a significant decrease in diastolic blood pressure during L-arginine infusion, with reduced blood pressure variability and increased day-night differences.
Conclusions:
- Intravenous L-arginine administration effectively lowers systemic blood pressure in hypertensive patients, mediated through nitric oxide synthesis.
- The blood pressure-lowering effect of L-arginine appears transient, primarily occurring during the infusion period.
- Reduced blood pressure variability following L-arginine infusion suggests potential improvements in baroreceptor sensitivity or autonomic nervous system function.
Abstract:
BACKGROUND: The role of nitric oxide (NO) in regulation of systemic blood pressure both in normotensives and in hypertensives remains unknown. OBJECTIVE: To investigate the influence of L-arginine (the substrate for generation of NO) on blood pressure in 30 men (aged 51.5 +/- 7.3 years) with established primary arterial hypertension that was not well controlled. METHODS: The antihypertensive therapy was not discontinued and the patients were administered beta-blockers and calcium antagonists only. On day '0' the patients were administered 250 ml 0.9% NaCl during 180 min intravenously. Then we infused 250 mg/kg L-arginine diluted in 250 ml 0.9% NaCl over 180 min into the antecubital vein for four consecutive days (days 'I'-'IV'). Conventional blood pressure and heart rate measurementws were performed before infusion and every 30 min during infusion. Twenty-four-hour ambulatory blood pressure monitoring (with a SpaceLabs 90207 device) with half-hourly recordings during the daytime and during the night-time was performed on the day of NaCl infusion ('0') and repeated on the day of L-arginine infusion ('II') for all patients. As indicators of generation of NO, blood level of cyclic GMP and urinary concentration of nitrite/nitrate were measured. RESULTS: On all days of L-arginine infusion we found significant falls in systolic and diastolic blood pressures (P < 0.0001) with an accompanying significant increase in heart rate (P < 0.001). The most potent hypertensive effect during infusion of L-arginine was observed on day 'I'. Mean systolic blood pressure decreawsed from 152.1 +/- 20.0 mmHg to a minimum of 123.3 +/- 16.2 mmHg after 60 min of the infusion (by about 19%). The maximal percentage fall in systolic blood pressure was consecutively lower on each day oif L-arginine infusion. It was 14.3% on day 'II', 11.9% on day 'III' and 10.1% on day 'IV'. Similarly, the greatest reduction of diastolic blood pressure was observed during infusion of L-arginine on day 'I'. Mean diastolic blood pressure decreased from 95.9 +/- 13.6 to 80 +/- 9.7 mmHg after 120 min of infusion (by about 17%). On the consecutive days maximal falls in diastolic blood pressure compared with its initial value were 13.5% on day 'II', 10.4% on day 'III' and 9.8% on day 'IV'. Twenty-four-hour ambulatory blood pressure monitoring revealed a significant decrease in diastolic blood pressure during infusion of L-arginine compared with day 0 when 0.9% NaCl was infused. Systolic and diastolic blood pressure variabilities were significantly decreased and the day-night differences in systolic and diastolic blood pressures were increased after infusion of L-arginine. We found a significant correlation between heart rate and systolic blood pressure both during the daytime and during night-time on the day of infusion of L-arginine. An increase in urinary concentration of nitrite/nitrate was observed after administration of L-arginine.CONCLUSION: The present results demonstrate that infusion of L-arginine can influence the systemic blood pressure in hypertensives through NO synthesis. By using ambulatory blood pressure monitoring we documented that the hypotensive effect of L-arginine seems to be limited to the infusion period itself. A decrease in blood pressure variability might imply an increase in sensitivity of baroreceptors or an improvement of autonomic functioning.