Cyclooxygenase inhibition and baroreflex sensitivity in humans

Monahan, Kevin D.; Ray, Chester A.

doi:10.1152/ajpheart.00357.2004

Cited by 21 publications

(31 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, thromboxane B 2 values were decreased after the ketorolac infusion during baseline as well as after exercise, suggesting that prostaglandin synthesis was attenuated after ketorolac administration (Table 1). These observations are consistent with previous work (5,21,35,54).…”

Section: Discussionsupporting

confidence: 94%

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

Momen¹,

Cui²,

McQuillan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 94%

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

Momen¹,

Cui²,

McQuillan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Notwithstanding these limitations, it should be noted that rats of the present study showed reasonably low HR values (Ͻ400 beats/min), which is a good indicator of an acceptable level of surgical stress, possibly owing to the administration of a long-acting nonsteroidal anti-inflammatory drug before surgery. It is important to note that this class of drugs has been reported not to impair the baroreceptor sensitivity in rats (28) or the sympathetic BRS in humans (21).…”

Section: Discussionmentioning

confidence: 96%

Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

Kanbar

Chapuis²,

Oréa³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Kanbar R, Chapuis B, Oréa V, Barrès C, Julien C. Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats. Am J Physiol Regul Integr Comp Physiol 295: R8 -R14, 2008. First published April 30, 2008 doi:10.1152/ajpregu.00147.2008This study compared the baroreflex control of lumbar and renal sympathetic nerve activity (SNA) in conscious rats. Arterial pressure (AP) and lumbar and renal SNA were simultaneously recorded in six freely behaving rats. Pharmacological estimates of lumbar and renal sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was significantly (P Ͻ 0.05) lower for lumbar [3.0 Ϯ 0.4 normalized units (NU)/mmHg] than for renal (7.6 Ϯ 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar and renal BRS were continuously assessed by computing the gain of the transfer function relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer gain was considered only when coherence between AP and SNA significantly differed from zero, which was verified in 99 Ϯ 1 and 96 Ϯ 3% of cases for lumbar and renal SNA, respectively. When averaged over the entire baseline period, spontaneous BRS was significantly (P Ͻ 0.05) lower for lumbar (1.3 Ϯ 0.2 NU/mmHg) than for renal (2.3 Ϯ 0.3 NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation coefficients were 26 Ϯ 2 and 28 Ϯ 2% for lumbar and renal SNA, respectively). These fluctuations were positively correlated in five of six rats (R ϭ 0.44 Ϯ 0.06; n ϭ 204 Ϯ 8; P Ͻ 0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA shows quantitative differences but is modulated in a mostly coordinated way. arterial pressure; baroreceptor reflex; sympathetic nervous system; transfer function THE ARTERIAL BARORECEPTOR reflex plays a major role in the short-term control of arterial pressure (AP) mainly through the modulation of efferent sympathetic nerve activity (SNA) to regional circulations (12). In rats, studies aimed at characterizing the baroreflex control of SNA under physiological conditions, i.e., in the conscious state, have been based mostly on recordings of renal SNA (RSNA;3,5,7,10,13,16,20,23,25), mainly because of the purely postganglionic nature of this activity. Most often, authors implicitly assumed that RSNA provided a reliable reflection of other regional SNAs. In the meantime, evidence has accumulated suggesting a differential baroreflex control of regional SNAs in several animal species (22). In the rat, the comparison of the baroreflex control of regional SNAs has been carried out in urethane-chloralose anesthetized animals by using the vasoactive drug injection technique, i.e., the so-called pharmacological method (29,30). In these studies, it was reported that the characteristics of the baroreflex function curves differed between RSNA, lumbar SNA (LSNA), and adrenal SNA. In conscious rats, this information has not...

show abstract

“…Despite a decline in ejection fraction and an increase in end systolic volume in the CM-COX2 KOs, heart rate was suppressed rather than increased via baroreflex activation when compared to controls. Infusion or application of prostaglandins to the carotid sinus have variously been reported to magnify (37) or attenuate (38,39) the baroreflex response, although the relevance of these observations in humans has been questioned (40).…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Wang

Patel

Ricciotti

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

108

105

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs selective for inhibition of COX-2 increase heart failure and elevate blood pressure. The COX-2 gene was floxed and crossed into merCremer mice under the ␣-myosin heavy-chain promoter. Tamoxifen induced selective deletion of COX-2 in cardiomyocytes depressed cardiac output, and resulted in weight loss, diminished exercise tolerance, and enhanced susceptibility to induced arrhythmogenesis. The cardiac dysfunction subsequent to pressure overload recovered progressively in the knockouts coincident with increasing cardiomyocyte hypertrophy and interstitial and perivascular fibrosis. Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2.arrhythmia ͉ heart failure ͉ knockout ͉ NSAIDs ͉ fibrosis R andomized, placebo-controlled trials indicate that nonsteroidal antinflammatory drugs (NSAIDs) specific for inhibition of cyclooxygense (COX)-2 confer an increased risk of myocardial infarction and stroke (1-5), effects explicable by suppression of COX-2-derived products, such as prostacyclin (PGI 2 ) and prostaglandia E 2 (PGE 2 ) (6). While, the clinical spectrum of hazard is dominated by a predisposition to thrombosis, an additional feature has been congestive heart failure (1-4). NSAIDs may variably increase blood pressure (7): studies in rodents (8, 9) and a meta-analysis of clinical studies (10) suggest that this reflects inhibition of COX-2 and the specificity with which this is attained (11). Elevation of blood pressure by manipulation of the prostaglandin pathway is conditioned by genetic background in rodents (12). However, given this caveat, deletion or inhibition of COX-2 (8, 13) and deletion of the E prostanoid (EP)-2 receptor (14, 15) or the I-prostanoid receptor (IP) (16) for the COX-2 products, PGE 2 and PGI 2 respectively, may each result in hypertension. Indeed, deletion of the IP in these mice also results in cardiac hypertrophy and fibrosis, effects ameliorated by coincident deletion of the receptor for thromboxane A 2 , the TP, a maneuver that does not, alone, affect blood pressure (16). By contrast, inhibition or deletion of COX-1 attenuates the hypertensive response to infusion of angiotensin II (8) or treatment with a COX-2 inhibitor (13). Although placebo-controlled trials provide unequivocal evidence that COX-2-specific NSAIDs confer a cardiovascular hazard, the number of events within each trial are insufficient to permit analysis of covariates. Thus, it is unknown whether congestive heart failure on NSAIDs results solely from or is exacerbated by hypertension.Although suppression of COX-2-derived prostanoids is sufficient to explain the cardiovascular hazard conferred by purposedesigned and older NSAIDs specific for inhibition of COX-2 (17), there has been interest in the possibility that some or all of these effects might reflect ''off target'' effects. One such example was an overview-trial analysis interpreted to suggest that arrhythmia, cardiac arrest, ...

show abstract

Cyclooxygenase inhibition and baroreflex sensitivity in humans

Cited by 21 publications

References 41 publications

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

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

Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Contact Info

Product

Resources

About