Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition.

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake, specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed three 5-min bouts of light knee-extensor exercise. Skeletal muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA), and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L-NMMA and indomethacin. At rest, inhibition of NOS alone and in combination with indomethacin reduced (P < 0.05) muscle blood flow. NOS inhibition increased (P < 0.05) limb oxygen extraction fraction (OEF) more than the reduction in muscle blood flow, resulting in an ∼20% increase (P < 0.05) in resting muscle oxygen consumption. During exercise, muscle blood flow and oxygen uptake were not altered with NOS inhibition, whereas muscle OEF was increased (P < 0.05). NOS and COX inhibition reduced (P < 0.05) blood flow in working quadriceps femoris muscle by 13%, whereas muscle OEF and oxygen uptake were enhanced by 51 and 30%, respectively. In conclusion, by specifically measuring blood flow and oxygen uptake by the use of PET instead of whole limb measurements, the present study shows for the first time in humans that inhibition of NO formation enhances resting muscle oxygen uptake and that combined inhibition of NOS and COX during exercise increases muscle oxygen uptake.

Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina.

The aim of this study was to compare the efficacy and safety of continuous and intermittent transdermal nitrate therapy using ambulatory electrocardiographic (Holter) monitoring. Eighty-five patients with stable angina pectoris and positive exercise test results participated during their concomitant antiischemic medication in a randomized open trial lasting 12 weeks. After a 3-week run-in period with continuous therapy (10 mg/24 hours), patients were randomized to either continuous- or intermittent-therapy groups. In the intermittent-therapy group the patients removed their patch at night (the mean patch-off period was 10 hours). Forty-eight-hour Holter monitoring was performed in each patient after randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in each group. A total of 11,194 hours of electrocardiography were recorded and 607 ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared during daytime. The number of ischemic episodes per 48 hours with intermittent therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2 weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not statistically significant because a large number of patients (30%) had no ischemic episodes on Holter recording. However, when examining 47 patients with episodes during the study, the number of episodes was significantly reduced in the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in asymptomatic and symptomatic episodes were concordant. No changes and differences between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED AT 250 WORDS)