Enhanced resistance artery sensitivity to agonists under isobaric compared with isometric conditions.
We have compared the responsiveness of rabbit mesenteric resistance arteries with agonists under isometric and isobaric conditions. When pressurized (60 mmHg), arteries spontaneously reduced their diameter by 18.1%. An equivalent isometric stress did not generate force in a "wire" myograph. Subsequently, much higher concentrations of norepinephrine (NE) and histamine were required to cause isometric contractions than were needed to reduce vascular diameter of pressurized vessels, whereas angiotensin II produced a maintained response only in pressurized arteries. Reducing transmural pressure to 20 mmHg abolished pressure-induced myogenic tone and decreased arterial sensitivity to NE. Under isometric conditions, partial depolarization with KCl increased sensitivity to NE and histamine to within the concentration range effective in pressurized vessels and also "revealed" responses to angiotensin II. The membrane potential of the vascular smooth muscle cells under partially depolarized conditions was similar to that found in vivo and in vessels studied isobarically. These observations demonstrate a fundamental interaction between pressure-induced myogenic tone and the sensitivity of resistance arteries to vasoactive stimuli. This influence was mimicked in isometrically mounted vessels by partial depolarization, indicating a possible pivotal role for membrane potential in determining the reactivity of the resistance vasculature.
Dunn
W R
WR
Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405.
Wellman
G C
GC
Bevan
J A
JA
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006632:Histamine / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010812:Physical Stimulation; D011312:Pressure; D011817:Rabbits; D014655:Vascular Resistance; D014661:Vasoconstriction
D000804:Angiotensin II; D006632:Histamine; D009638:Norepinephrine