Histamine H2 receptor blockade augments blood pressure responses to acute submaximal exercise in males

Hyung-Woo Doh, Charles L. Stebbins, Hyun-Min Choi, Joonsung Park, Hosung Nho, Jong-Kyung Kim
2016 Applied Physiology, Nutrition and Metabolism  
Histamine is a potent vasodilator that has been found to increase during exercise. We tested the hypothesis that histamine attenuates blood pressure, cardiac output (CO) and vascular resistance responses to short term, submaximal dynamic exercise during H 2 receptor blockade. Fourteen healthy men (20-29 yr) were studied. Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressure and heart rate (HR) were assessed at rest and during the last min of 10 min of submaximal cycling
more » ... mal cycling exercise (60% of V0 2peak ) in the absence and presence of histamine H 2 receptor blockade (ranitidine, 300 mg). Stroke volume (SV) (impedance cardiography) and plasma norepinephrine (NE) were measured and CO, rate x pressure product (RPP) and total peripheral resistance (TPR) were calculated. Plasma levels of histamine were also measured. H 2 blockade had no effects on any variables at rest. During exercise, SBP (184± 3 vs. 166±2 mmHg), MAP (121±2 vs. 112±5 mmHg), RPP (25.9±0.8 x 10 3 vs. 23.5±0.8.0 x 10 3 mmHg • beats/min) were greater during blocked conditions (P<0.05) and an interaction was observed for TPR. SV, DBP, HR and NE levels were unaffected by blockade. Plasma histamine increased from 1.83 ± 0.14 ng/ml at rest to 2.33 ± 0.23 ng/ml during exercise (P<0.05) and was not affected by H 2 blockade (1.56 ± 0.23 vs. 1.70 ± 0.24 ng/ml). These findings suggest that, during submaximal exercise, histamine attenuates blood pressure, vascular resistance and work of the heart via activation of H 2 receptors, and that these effects primarily occurred in the vasculature and not in the myocardium. Page 13 of 25 https://mc06.manuscriptcentral.com/apnm-pubs Applied Physiology, Nutrition, and Metabolism 1990). Complicating the situation is the fact that histamine can also be produced acutely (without being stored) by non-mast cells via the decarboxylation of histidine via histidine decarboxylase (Watanabe and Ohtsu, 2002). Due to these multiple pathways, it is presently not clear what mechanisms are responsible for the release of histamine during exercise. However, Halliwill et al. (2013) pointed out that factors associated with exercise, such as reactive oxygen species, cytokines and elevated body temperature, have been linked to mast cell degranulation. Limitations to the Study The primary limitation to the study was the fact that we did not measure regional blood flow, as it is very difficult to assess accurately and non-invasively in humans during dynamic exercise. Consequently, we were not able to determine the regional circulations affected by H 2 receptor blockade that may have contributed to the concomitant increases in TPR Page 16 of 25 https://mc06.manuscriptcentral.com/apnm-pubs Applied Physiology, Nutrition, and Metabolism cycyle on hemodynamic responses during dynamic exercise in sedentary women. Korean J. Physiol. Pharmacol. 17(6): 499-503. Colombo, F., Porro, T., del Rosso, G., Bertalero, P., Orlandi, L., and Libretti, A. 1989. Cardiovascular responses to physical exercise and tyramine infusion in hypertensive and normotensive subjects. J. Hum. Hypertens. 3(4): 245-349. . 1985. Pharmacokinetics of ranitidine following oral administration with ascending doses and with multiple-fixed doses J. Clin. Pharmacol. 25(6): 437-443.
doi:10.1139/apnm-2015-0450 pmid:27191340 fatcat:p7q275qux5gpzhd2u3u4fuuozi