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Epinephrine Regulation of Hemodynamics in Catecholamine Knockouts and the Pithed Mouse
Author(s) -
Sun Ping,
Bao Xuping,
Elayan Hamzeh,
Milic Milos,
Liu Fujun,
Ziegler Michael G.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1410.078
Subject(s) - endocrinology , medicine , phenylethanolamine , epinephrine , phenylethanolamine n methyltransferase , blood pressure , stimulation , phenylephrine , agonist , chemistry , dopamine , tyrosine hydroxylase , receptor
Phenylethanolamine N‐methyltransferase (PNMT) catalyzes synthesis of epinephrine (E) and is present in the brain, heart, and adrenal. E is a neurotransmitter and important hormone; however, its role in regulating cardiovascular dynamics is still unclear. We generated an E‐deficient mouse model by knocking out the PNMT gene. The PNMT KO mouse had normal resting blood pressure, while treadmill exercise caused hypertension, suggesting an impaired response to stress in the absence of the stress hormone E. As PNMT occurs at a lower concentration in many extra‐adrenal tissues including the brain, we set up a pithed mouse model to study the peripheral effects of E on cardiovascular dynamics, using pithing to eliminate central and reflex effects. The pithed mouse requires different surgical techniques and stimulation voltages than rats, and showed voltage‐ and frequency‐dependent blood pressure responses to electrical stimuli. Stimulation with the α‐adrenergic agonist phenylephrine gave a marked systolic pressor response, while the β2 agonist salbutamol lowered diastolic blood pressure. The pithed PNMT KO mouse had an exaggerated blood pressure response to salbutamol, suggesting β2 receptor supersensitivity. A targeted KO of tyrosine hydroxylase in PNMT‐producing cells produced a mouse deficient in catecholamines in the adrenal. These targeted KO mice displayed significantly smaller pressor responses than pithed control mice. We find that E release during stress prevents an excessive increase in blood pressure.