Twik‐2−/− mouse demonstrates pulmonary vascular heterogeneity in intracellular pathways for vasocontractility

Autor:	David J. Durgan, Julia O. Reynolds, Robert M. Bryan, Harry Karmouty-Quintana, Lavannya M. Pandit, George G. Rodney, Melanie G. Kitagawa
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Male medicine.medical_specialty Pulmonary Circulation Physiology Myocytes Smooth Muscle Action Potentials 030204 cardiovascular system & hematology Pulmonary Artery Cardiovascular Physiology Calcium in biology Potassium channels 03 medical and health sciences Mice Phenylephrine 0302 clinical medicine Potassium Channels Tandem Pore Domain Smooth Muscle Physiology (medical) medicine.artery Internal medicine Membrane Physiology pulmonary hypertension medicine Animals Vasoconstrictor Agents Cells Cultured Original Research Membrane potential Chemistry Wild type medicine.disease Pulmonary hypertension Potassium channel Mice Inbred C57BL Endocrinology vasocontractility Vasoconstriction 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Pulmonary artery Calcium Muscle Contraction and Relaxation pulmonary artery smooth muscle cells 030217 neurology & neurosurgery Intracellular medicine.drug
Zdroj:	Physiological Reports
ISSN:	2051-817X
Popis:	We have previously shown Twik‐2−/− mice develop pulmonary hypertension and vascular remodeling. We hypothesized that distal pulmonary arteries (D‐PAs) of the Twik‐2−/− mice are hypercontractile under physiological venous conditions due to altered electrophysiologic properties between the conduit and resistance vessels in the pulmonary vascular bed. We measured resting membrane potential and intracellular calcium through Fura‐2 in freshly digested pulmonary artery smooth muscles (PASMCs) from both the right main (RM‐PA) and D‐PA (distal) regions of pulmonary artery from WT and Twik‐2−/− mice. Whole segments of RM‐PAs and D‐PAs from 20 to 24‐week‐old wildtype (WT) and Twik‐2−/− mice were also pressurized between two glass micropipettes and bathed in buffer with either arterial or venous conditions. Abluminally‐applied phenylephrine (PE) and U46619 were added to the buffer at log increments and vessel diameter was measured. All values were expressed as averages with ±SEM. Vasoconstrictor responses did not differ between WT and Twik‐2−/− RM‐PAs under arterial conditions. Under venous conditions, Twik‐2−/− RM‐PAs showed an increased sensitivity to PE with a lower EC50 (P = 0.02). Under venous conditions, Twik‐2−/− D‐PAs showed an increase maximal vasoconstrictor response to both phenylephrine and U46619 compared to the WT mice (P
Databáze:	OpenAIRE
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