will take place on Tuesday, 15 May 2018 from 17:15 to 18:15 hours in CBBM, Ground Floor, B1/B2.
Host: Prof. Dr. Markus Schwaninger
Institute of Experimental and Clinical Pharmacology and Toxicology
University of Lübeck
Abstract
Acid-base disturbances are common during disease, particularly when local blood flow is insufficient to meet the metabolic demand.
NBCn1-mediated Na+,HCO3–-cotransport and NHE1-mediated Na+/H+-exchange protect vascular endothelial cells against intracellular acidification. Low intracellular pH of endothelial cells inhibits NO production, attenuates endothelium-dependent vasorelaxation, and deregulates myogenic tone. Mice with chronically reduced intracellular pH also show disturbed blood pressure regulation.
In addition, inhibition of Cl–/HCO3–-exchange—that causes intracellular alkalinization of endothelial cells—decreases gap-junctional intercellular communication and endothelium-dependent hyperpolarizations.
Extracellular acid-base disturbances contribute to metabolic regulation of vascular tone but the sensing and signaling mechanisms have been unresolved. Due to chemical equilibration between H+, HCO3–, and CO2, their individual signaling roles have been difficult to evaluate. In order to independently control pH, [HCO3–], and pCO2, we use out-of-equilibrium CO2/HCO3– solutions based on instantaneously mixed precursor solutions of dissimilar CO2/HCO3–/pH compositions. Selective decreases in extracellular [HCO3–], at fixed pH of 7.4 and CO2 of 5%, increase the contractile response of cerebral arteries through a mechanism that depends on receptor protein tyrosine phosphatase (RPTP)γ. RPTPγ is a transmembrane protein with homology to the carbonic anhydrases. Under equilibrated CO2/HCO3– conditions, RPTPγ regulates endothelium-dependent vasorelaxation and mediates a net braking action on vasorelaxation elicited by metabolic acidosis. In congruence, knockout of RPTPg modifies cerebral blood flow responses to sensory stimuli and hyperventilation.
In this talk, I will discuss the dual roles of HCO3– and H+ in the vascular wall where they a) provide substrate for membrane transporters that control intracellular pH and maintain normal endothelial function and b) modify vascular responses to acid-base disturbances.
Biosketch
Ebbe Boedtkjer is Associate Professor of Physiology at the Department of Biomedicine, Aarhus University, Denmark. He received his MD (2009) and PhD (2010) degrees from Aarhus University, and spent part of his PhD-studies at Case Western Reserve University, USA. In 2011, he became Assistant Professor of Physiology at Aarhus University; and in 2013, he was appointed Associate Professor at the same institution.
Dr. Boedtkjer’s research focuses on the consequences and underlying mechanisms of acid-base-mediated regulation of resistance artery tone, blood pressure, and cerebral blood flow with particular focus on transporters and sensors of acid-base equivalents. He also explores consequences of the disturbed local environment in cancer tissue where acid-base conditions are fundamentally altered due to the high metabolic activity of the cancer cells.
