Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans

Abstract

Momen A, Cui J, McQuillan P, Sinoway LI. Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans. Am J Physiol Heart Circ Physiol 294: H2184-H2190, 2008. First published March 7, 2008 doi:10.1152/ajpheart.00948.2007.-During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI ϩ stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI ϩ stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI ϩ stretch than during PHGMI alone (P Ͻ .01). Similar results were found after a saline Bier block trial (⌬53 Ϯ 13% vs. ⌬35 Ϯ 10%; P Ͻ 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI ϩ stretch than during PHGMI alone [⌬39 Ϯ 8% vs. ⌬40 Ϯ 12%; P ϭ not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI ϩ stretch (P ϭ NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins. kidney; exercise; nervous system; sympathetic; muscle metabolite EXERCISE ACTIVATES THE sympathetic nervous system (SNS) that contributes to increases in heart rate (HR), blood pressure, ventilation, and peripheral vascular resistance. These adjustments are essential for adequate perfusion of vital organs, e.g., skeletal muscle, heart, and brain (31). Work by Alam and Smirk (1) more than half a century ago suggested that during exercise, muscle metabolites accumulate in active skeletal muscle and that when these metabolites are trapped in the muscle during a period of postexercise circulatory arrest, a pressor reflex is evoked, presumably by direct stimulation of metabolite sensitive afferents in the muscle. This response has been termed the "muscle metaboreflex" (3,23,32,38,43). It has been further demonstrated that stimulation of mechanically sensitive afferents during muscle contraction activates the SNS (18, 19, 52) and evokes vasoconstriction. This response has been termed the "muscle mechanoreflex." O...

Effect of oxidative stress on sympathetic and renal vascular responses to ischemic exercise

“…These findings are consistent with previous studies from our laboratory (Momen et al. , ) and others (Kuipers et al. ) characterizing acute changes in renal vascular tone in response to isometric handgrip exercise.…”

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

“…The majority of studies in healthy humans have shown that inhibiting exercise-induced prostanoid synthesis attenuates reflex cardiovascular responses (7,8,14,23,25). These studies all used handgrip exercise, and they all administered either indomethacin or ketoprofen.…”

“…A different study (36) in cats showed that intravenous indomethacin attenuated the rise in MAP in response to static hindlimb contraction. Many studies (7,8,14,23,25) in healthy humans have demonstrated that blocking the prostanoid pathway attenuates reflex cardiovascular responses to exercise, although two studies (9, 12) have contradicted these findings. Currently, it is believed that prostanoids are especially important for sensitizing group III afferents during low-intensity dynamic exercise (i.e., before the onset of muscle metaboreflex activation).…”

A role for nitric oxide within the nucleus tractus solitarii in the development of muscle mechanoreflex dysfunction in hypertension

“…Although it is tempting to interpret findings elicited during passive stretch as being directly representative of mechanoreflex activity, conclusions must be tempered with this limitation in mind. It should be noted that ideologically similar passive stretching techniques have recently been used in humans to elucidate the muscle mechanoreflex contribution to cardiovascular control (Fisher et al 2005; Cui et al 2006, 2008 a , b , 2010; Drew et al 2008 a , b ; Momen et al 2008). Results from these studies have proved invaluable in extending the findings from animal investigation to humans.…”

“…Given that static exercise is only one form of physical activity, it will be important to determine whether the findings reported in this investigation are valid for more dynamic manipulations of the muscle mechanoreflex. In addition, several studies in animals (Rotto et al 1990; Adreani & Kaufman, 1998) and humans (Bell & White, 2005; Cui et al 2008 a , b ; Momen et al 2008) have demonstrated that muscle metabolites sensitize mechanoreceptors. Whether this relationship is altered in hypertension remains to be determined, as does the role of centrally produced NO in processing this afferent information.…”