Cyclooxygenase inhibition and baroreflex sensitivity in humans.
Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults.
Monahan
Kevin D
KD
Department of Medicine (Cardiology), General Clinical Research Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-2390, USA. kmonahan@psu.edu
Ray
Chester A
CA
D000293:Adolescent; D000328:Adult; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D020910:Ketorolac / Q000008:administration & dosage*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D020910:Ketorolac