Effects of insulin on the acetylcholine-induced hyperpolarization in the guinea pig mesenteric arterioles.
BACKGROUND
Insulin induces endothelium-dependent vasodilatation, which may be casually related to the insulin resistance and hypertension. Endothelium-derived nitric oxide (NO) is the most important mechanism of insulin-induced vasodilatation, and a possible contribution of endothelium-derived hyperpolarizing factor (EDHF) is also considered. Attempts were made to observe the effects of insulin on acetylcholine (ACh)-induced hyperpolarization in the submucosal arteriole of the guinea pig ileum, the objective being to investigate possible involvement of EDHF in the actions of insulin.


METHODS
Conventional microelectrode techniques were applied to measure the membrane potential of smooth muscle cells in the submucosal arteriole. EDHF-induced hyperpolarization was elicited by ACh in the presence of both N(omega)-nitro-L-arginine (L-NNA) (100 microM) and diclofenac (1 microM).


RESULTS
The resting membrane potential was -70.9 mV, and Ba(2+) (0.5 mM) depolarized the membrane to -33.0 mV. Insulin (10 microU/ml to 100 mU/ml) did not change the membrane potential in the absence or presence of Ba(2+). In the presence of Ba(2+), ACh (3 microM) hyperpolarized the membrane with two components, an initial large hyperpolarization followed by a slow and small one. Low concentration of insulin (100 microU/ml) did not alter the ACh-induced hyperpolarization. High concentration of insulin (100 mU/ml) shortened the time required to reach the peak amplitude and tended to increase the peak amplitude of the ACh-induced hyperpolarization.


CONCLUSIONS
The data show that insulin enhances the ACh-induced hyperpolarization in the submucosal arterioles of the guinea pig ileum. The results suggested that EDHF also accounts for one of the endothelial factors involved in the insulin-induced vasodilatation.
Imaeda
Kenro
K
Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. kimaeda@med.nagoya-cu.ac.jp
Okayama
Naotsuka
N
Okouchi
Masahiro
M
Omi
Hitoshi
H
Kato
Takashi
T
Akao
Masaya
M
Imai
Seiji
S
Uranishi
Hiroaki
H
Takeuchi
Yoshiyuki
Y
Ohara
Hirotaka
H
Fukutomi
Tatsuya
T
Joh
Takashi
T
Itoh
Makoto
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D004008:Diclofenac / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007328:Insulin; D004008:Diclofenac; D000109:Acetylcholine