Ischemic exercise hyperemia in the human forearm: reproducibility and roles of adenosine and nitric oxide

Abstract

The roles of local metabolites in reactive and exercise hyperemia remain incompletely understood. A maximum metabolic stimulus caused by ischemic exercise (IE) could potentially fully activate all vasodilator pathways and limit potential redundancy amongst vasoactive substances. We tested the hypotheses that IE elicits a reproducible hyperemic response in the forearm and that adenosine (ADO) and nitric oxide (NO) contribute to this response. In separate protocols, forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and rhythmic forearm handgrip exercise (performed during last 2 min of ischemia). In protocol 1 (n = 8), FBF was measured after three trials of IE. In protocol 2 (n = 9), subjects performed IE during control (saline), aminophylline (APH; adenosine receptor antagonist), and combined APH/N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) infusions. In protocol 1, coefficients of variation for total (area under the curve) ΔFBF and ΔFVC (forearm vascular conductance) following IE were 10.4 ± 1.0% and 14.9 ± 1.0%, respectively. In protocol 2, peak ΔFBF was similar for saline and APH trials. Peak ΔFBF for the APH+L: -NMMA trial was greater than that of the APH trial (P = 0.03), and peak ΔFVC was marginally non-significant (P = 0.053). Total ΔFBF (54.8 ± 3.9, 55.2 ± 5.4, and 60.4 ± 4.8 ml 100 ml(-1); P = 0.43) and ΔFVC (51.4 ± 3.5, 52.1 ± 5.5, and 56.5 ± 5.0 ml 100 ml(-1) 100 mmHg(-1); P = 0.52) were similar for saline, APH, and APH+L: -NMMA, respectively. Our data suggest that (1) the hyperemic response to IE is reproducible and (2) inhibition of ADO alone or combined ADO and NO does not blunt the hyperemic response following IE.

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

“…3, this was not the case. With the experiments described here and others performed recently, it has become increasingly clear that individually ADO, NO, and PGs are not obligatory for the marked hyperemic response seen following a maximal metabolic stimulus (Lopez et al 2012). Furthermore, combined ADO/NO and NO/PG blockade does not blunt the hyperemic response to IE.…”

“…We have previously discussed the possibility of an ischemic preconditioning effect from the earlier bouts of IE influencing the blood flow responses to subsequent responses. In this context, repeated bouts of IE alone show that sequential bouts elicit a reproducible response that tends to rise with additional trial (Lopez et al 2012).…”

“…In addition, it could be related to the local versus systemic blockade. A review of the repeatability data for this ischemic exercise model showed a trend of increasing baseline blood flow for each successive trial that may have masked effects of drug infusion on baseline flow (Lopez et al 2012). This was despite evidence from Doppler ultrasound studies using beat-to-beat blood velocity measures that a 20-min resting period was adequate for blood flow to return to baseline following handgrip exercise (Casey and Joyner 2011).…”

“…Amongst these, adenosine (ADO), nitric oxide (NO), and prostaglandins (PGs), particularly PGI 2 (prostacyclin), have drawn much interest from investigators. We have previously investigated the roles and interaction of ADO and NO in the response to IE and found that blockade of ADO alone or of both ADO and NO synthase did not reduce the overall response (Lopez et al 2012). These results indicated that ADO and NO are not solely responsible or even obligatory to the vasodilator response in these settings.…”

“…Compared to ischemia alone, ischemic exercise (IE) elicits an overall larger hyperemic response (Sinoway et al 1986;Wendelhag et al 1999;Lopez et al 2012). …”