Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats.
Increased sympathetic nervous activity (SNA) elevates venomotor tone in deoxycorticosterone acetate (DOCA)-salt hypertension. We studied the mechanisms by which the SNA increases venomotor tone in DOCA-salt hypertension by making in situ intracellular recordings of venous smooth muscle cell (VSMC) membrane potential (E(m)) and measurement of outside diameter (OD) in mesenteric veins (MV) and mesenteric arteries (MA) of anesthetized rats. We also studied norepinephrine (NE)- and endothelin-1 (ET-1)-induced increases in MA or MV perfusion pressure (PP) in vitro. E(m) in DOCA-salt MV was depolarized compared with sham MV. Prazosin hyperpolarized VSMC E(m) in DOCA-salt but not in sham MV. NE concentration-response curves (CRCs) for OD decreases in MV from DOCA-salt rats were left-shifted with an increased maximum response (E(max)) compared with sham MV. NE CRCs for OD decreases in MA were right-shifted with reduced E(max) in DOCA-salt compared with sham rats. ET-1 CRCs were similar in DOCA-salt and sham MV but were right-shifted with reduced E(max) in DOCA-salt MA. NE CRCs for MAPP increases were left-shifted without a change in E(max) in DOCA-salt rats. NE did not change MVPP. MAPP and MVPP for ET-1 CRCs were similar in sham and DOCA-salt rats, but E(max) for MAPP was reduced in DOCA-salt rats. Hematoxylin staining revealed hypertrophy in DOCA-salt MA but not in MV. We conclude that there is increased reactivity to NE released from the sympathetic nervous system in DOCA-salt MV that causes VSMC depolarization and increased venomotor tone. In DOCA-salt rats, in vivo ET-1 reactivity is maintained in MV, but reduced in MA.
Xu
Hui
H
Department of Pharmacology & Toxicology, Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA. xuhui2@msu.edu
Fink
Gregory D
GD
Galligan
James J
JJ
D000818:Animals; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D003900:Desoxycorticosterone; D009638:Norepinephrine