Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails

Abstract

Vasodilatory mechanisms controlling post-exercise or post-ischemic hyperemia are thought to be under redundant control and remain incompletely understood. A maximal metabolic stimulus evoked by ischemic exercise (IE) might limit redundancy by full activation of multiple pathways. We tested whether nitric oxide (NO) and/or prostaglandins contribute to the hyperemic response to IE. 17 subjects were randomized into two groups and performed three trials of IE during control (saline), N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) (protocol 1) or ketorolac (cyclooxygenase inhibition) infusion (protocol 2), and combined L-NMMA/ketorolac infusion via a brachial arterial catheter. Forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and simultaneous rhythmic handgrip exercise (final 2 min). Peak and total (area under the curve) FBF and blood pressure (MAP) were measured for 3 min after each trial. Forearm vascular conductance (FVC) was calculated as FBF/MAP. Change (Δ) in peak FBF and FVC from baseline differed only between peak FBF for the saline and L-NMMA + ketorolac trials in protocol 1. Peak ΔFBF was 26.8 ± 2.5, 30.0 ± 2.8, and 33.9 ± 3.6 ml 100 ml(-1) min(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials (P = 0.04). For protocol 1 (n = 8), total ΔFVC was 59.6 ± 4.3, 57.8 ± 6.0, and 59.9 ± 5.6 ml 100 ml(-1) 100 mmHg(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials, (P = 0.82). For protocol 2 (n = 9), total ΔFVC was 54.2 ± 5.0, 56.9 ± 4.5, and 56.5 ± 5.3 ml 100 ml(-1) 100 mmHg(-1) for saline, ketorolac, and ketorolac + L-NMMA trials, (P = 0.69). These results suggest that NO and PGs are not obligatory for the hyperemic response to IE, and other vasodilator mechanisms predominate.

The effect of ageing and indomethacin on forearm reactive hyperaemia in healthy adults

“…; Lopez et al . ). The strain gauge was placed around the non‐dominant forearm at its greatest circumference (∼5 cm below the antecubital crease), with the forearm positioned above heart level.…”

“…; Lopez et al . ). Nevertheless, this vasodilatation appears to be driven in part by both endothelium‐derived NO and PGs, but there are conflicting reports on the extent to which postischaemic hyperaemic flow is affected by COX inhibition, with both increased and decreased flow being reported in young healthy adults (Kilbom & Wennmalm, ; Carlsson & Wennmalm, ; Carlsson et al .…”

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

“…FIGURE 19 shows analogous data from human forearm studies. In general, efforts to block multiple vasodilator pathways in skeletal muscle have demonstrated that the blood flow response to prolonged contractions is incredibly robust and difficult to reduce by more than ϳ20% under most circumstances (286,415). FIGURE 19 also demonstrates the critical importance of both the time resolution of the blood flow measurements in evaluating pharmacological approaches to blocking one or more dilator pathways and issues related to individual variability.…”

The effect of acute administration of Vitamin D on micro vascular endothelial function in Caucasians and South Asian Indians

“…But brachial artery dilation is mediated by shear receptors which activate through microvilli and a prostaglandin mediated process including the release of nitric oxide [44–46]. The local response to occlusion is not mediated by prostaglandins or nitric oxide [47]. The micro vascular response to heat is mediated by other mechanisms.…”