Abstracts of the XXXVIII Congress of the Spanish Society of Physiological Sciences (SECF), 13-16 September 2016, Zaragoza, Spain

• DOI: 10.1007/s13105-016-0508-2
• Publication Date: 2016-08-15T00:05:57Z
• Authors: Amaya Rando; Laura Moreno; Pilar Zaragoza; Janne M. Toivonen; Samanta Gasco; Ana C. Calvo; L. A. Moreno; Miriam de la Torre; Rosario Osta
• Keywords: 0301 basic medicine; 03 medical and health sciences; Physiology; Spain

Background and purpose: Endothelium-dependent vasodilation plays an important role in the regulation of vascular tone in different vascular beds. Besides the release of prostacyclin (PGI2) and nitric oxide (NO), the endothelium mediates vasodilation through endothelium-derived hyperpolarization (EDH). EDH is defined as the hyperpolarizing current through myoendothelial gap junctions that hyperpolarizes and relaxes the underlying vascular smooth muscle. EDH has been shown to play a major role in the modulation of preglomerular tone in the renal circulation. Here, we studied the functional expression of the different K+ channels involved in the EDH of renal arteries and its correlation with renal vasodilator responses. Material and methods: Segmental and interlobar arteries from the kidney of male Wistar rats were used in these experiments. Freshly isolated endothelial cells were obtained by scraping the luminal surface of the artery after enzymatic digestion with trypsin, and K+ currents were measured using the whole cell configuration of the patch clamp technique (Oliván-Viguera et al., Basic Clin. Pharmacol. Toxicol. Doi: 10.1111/bcpt.12560, 2016). Moreover, changes in isometric wall tension of the vessels were also studied using wire myography. Interlobar arteries were precontracted with phenylephrine (Phe) and acetylcholine (ACh) concentration-response curves were constructed under conditions of NO synthase- and cyclooxygenase blockade, in the absence and the presence ofvarious KCa channel blockers. Key results: Under Voltage-clamp conditions a change in the morphology of the currents -induced by ramps from - 100 mV to 160 mV; 600 ms- was observed in response to the addition of ACh, evidencing a selective activation of channels sensitive to increases in intracellular Ca2+ concentrations ([Ca2+]i). Blockers of KCa channels, Iberiotoxin, TRAM-34 and UCL 1648, were able to inhibit different components of those currents. Moreover, in the presence of L-NAME and indomethacin, Iberiotoxin and TRAM-34 inhibited ACh-induced vasodilatation ininterlobar arteries mounted in wire myographs.Conclusions and implications: The results show that KCa channels play a major role in the EDH of preglomerular renal circulation. BKCa, IKCa and SKCa are functionally expressed in the endothelial cells of segmental and interlobar arteries. Stimulation of endothelial cells with ACh has an effect mainly increasing IKCa currents, while basal levels of [Ca2+]i may allow SKCa currents to be active in the absence of ACh. BKCa and IKCa currents have an essential role in the vasodilatation induced by EDH, while SKCa currents might be mainly involved in the release of NO.Keywords: Renal arteries, EDH, KCa channels.