Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA318

Poster Communications

Differential enhancement of phenylephrine and histamine contractions of rabbit carotid arteries following Na+-K+ATPase inhibition

O. O. Arishe1,3, O. K. Uche1,3, A. B. Ebeigbe1,2

1. Department of Physiology, University of Benin, Benin City, Edo State, Nigeria. 2. Physiology, College of Medical Sciences, University of Benin, Benin City, Edo State, Nigeria. 3. Physiology, College of Medical Sciences, Benin City, Edo State, Nigeria.

Enhancement of agonist-induced contractions by Na+-K+ pump inhibition is dependent on the type of vasculature and agonists (Shelly, 2004; Matchkov et al, 2012). The goal of the present study was to examine the differences in contractions induced by phenylephrine (PE) and histamine following Na-K pump inhibition by K+-free exposure, in isolated rabbit carotid arteries. Ring segments of rabbit carotid arteries were obtained from New Zealand rabbits anesthetized with intravenous sodium pentobarbital (30mg/kg) and sacrificed by bleeding. Rings were suspended in 20ml organ baths containing physiological salt solution (PSS, bubbled with 95% O2, 5% CO2). Isometric contractions were recorded electronically at 370C, pH 7.4, under an initial load of 2g. We examined the concentration-response to phenylephrine in normal PSS as well as following 30min exposure to K+-free PSS. We also examined the effects of indomethacin (cyclooxygenase inhibitor) and L-NAME (NO synthase inhibitor) on the contractile responses to the agonists. Data were generated using a paired approach in which the same ring preparation was used for recording responses in normal PSS followed by K+-free PSS experiment. All preparations had intact endothelium. Following K+-free exposure, the concentration-response curves for both agonists were shifted to the left. Based on the EC50 and EC50 ratio values, the enhancement by K+-free exposure was significantly greater with phenylephrine contractions. The EC50 ratio for phenylephrine (normal: K+-free) was 46.30 while the value for histamine (normal : K+-free) was 5.08. Indomethacin (3 x 10-6M) but not L-NAME (1 x 10-5M) attenuated the enhancement by K+-free PSS of phenylephrine and histamine contractions. The respective magnitudes of enhancement of PE contractions in the absence or presence of indomethacin were: 29.74 ± 2.4 and 11.29 ± 3.1% (p<0.05, n = 5); whereas the respective values for histamine contractions (in the absence or presence of indomethacin) were: 9.25 ± 1.2 and 6.11 ± 0.7% (p<0.05, n = 5). While L-NAME had no effect on the enhanced PE and histamine contractions in K+-free PSS, indomethacin significantly attenuated the enhanced contractions by the agonists by 17.74 ± 2.4 and 3.14 ± 81% (p<0.05) respectively, for PE and histamine. We report that in K+-free PSS, in isolated rabbit carotid arteries, there is an endothelium-independent difference in enhancement of contractile responses to phenylephrine and histamine following Na-K pump inhibition, mediated in part, by prostaglandin. This study is of particular interest for understanding vascular pathophysiology associated with therapeutic use of digitalis drugs, which inhibit Na+-K+ ATPase.

Where applicable, experiments conform with Society ethical requirements