Abstract
1. Experiments were designed to investigate the mechanisms underlying the diabetes-related impairment of the vasodilatations of the perfused mesenteric arterial bed induced by acetylcholine (ACh) and K +. 2. In streptozotocin (STZ)-diabetic rats, the ACh-induced endothelium-dependent vasodilatation was attenuated. The dose-response curves for ACh in control and diabetic rats were each shifted to the right by N(G)-nitro-L-arginine (L-NOARG) and by isotonic high K + (60 mM). The ACh dose-response curves under isotonic high K + were not different between control and diabetic rats. 3. We also examined the vasodilatation induced by K +, which is a putative endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vasodilatation induced by a single administration of K + was greatly impaired in STZ-induced diabetic rats. Treatment with charybdotoxin plus apamin abolished the ACh-induced vasodilatation but enhanced the K +-induced response in controls and diabetic rats. After pretreatment with ouabain plus BaCl 2, the ACh-induced vasodilatation was significantly impaired and the K +-induced relaxation was abolished in both control and diabetic rats. 4. The impairment of the endothelium-dependent vasodilatation of the mesenteric arterial bed seen in STZ-induced diabetic rats may be largely due to a defective vascular response to EDHF. It is further suggested that K + is one of the endothelium-derived hyperpolarizing factors and that the vasodilatation response to K + is impaired in the mesenteric arterial bed from diabetic rats.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 549-556 |
| Number of pages | 8 |
| Journal | British Journal of Pharmacology |
| Volume | 130 |
| Issue number | 3 |
| State | Published - 2000 |
| Externally published | Yes |
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Keywords
- Diabetes
- Endothelium
- Endothelium-derived hyperpolarizing factor
- Mesenteric arterial bed
- Rat
- Streptozotocin
ASJC Scopus subject areas
- Pharmacology
Cite this
Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat. / Makino, Ayako; Ohuchi, Kunihiro; Kamata, Katsuo.
In: British Journal of Pharmacology, Vol. 130, No. 3, 2000, p. 549-556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat
AU - Makino, Ayako
AU - Ohuchi, Kunihiro
AU - Kamata, Katsuo
PY - 2000
Y1 - 2000
N2 - 1. Experiments were designed to investigate the mechanisms underlying the diabetes-related impairment of the vasodilatations of the perfused mesenteric arterial bed induced by acetylcholine (ACh) and K +. 2. In streptozotocin (STZ)-diabetic rats, the ACh-induced endothelium-dependent vasodilatation was attenuated. The dose-response curves for ACh in control and diabetic rats were each shifted to the right by N(G)-nitro-L-arginine (L-NOARG) and by isotonic high K + (60 mM). The ACh dose-response curves under isotonic high K + were not different between control and diabetic rats. 3. We also examined the vasodilatation induced by K +, which is a putative endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vasodilatation induced by a single administration of K + was greatly impaired in STZ-induced diabetic rats. Treatment with charybdotoxin plus apamin abolished the ACh-induced vasodilatation but enhanced the K +-induced response in controls and diabetic rats. After pretreatment with ouabain plus BaCl 2, the ACh-induced vasodilatation was significantly impaired and the K +-induced relaxation was abolished in both control and diabetic rats. 4. The impairment of the endothelium-dependent vasodilatation of the mesenteric arterial bed seen in STZ-induced diabetic rats may be largely due to a defective vascular response to EDHF. It is further suggested that K + is one of the endothelium-derived hyperpolarizing factors and that the vasodilatation response to K + is impaired in the mesenteric arterial bed from diabetic rats.
AB - 1. Experiments were designed to investigate the mechanisms underlying the diabetes-related impairment of the vasodilatations of the perfused mesenteric arterial bed induced by acetylcholine (ACh) and K +. 2. In streptozotocin (STZ)-diabetic rats, the ACh-induced endothelium-dependent vasodilatation was attenuated. The dose-response curves for ACh in control and diabetic rats were each shifted to the right by N(G)-nitro-L-arginine (L-NOARG) and by isotonic high K + (60 mM). The ACh dose-response curves under isotonic high K + were not different between control and diabetic rats. 3. We also examined the vasodilatation induced by K +, which is a putative endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vasodilatation induced by a single administration of K + was greatly impaired in STZ-induced diabetic rats. Treatment with charybdotoxin plus apamin abolished the ACh-induced vasodilatation but enhanced the K +-induced response in controls and diabetic rats. After pretreatment with ouabain plus BaCl 2, the ACh-induced vasodilatation was significantly impaired and the K +-induced relaxation was abolished in both control and diabetic rats. 4. The impairment of the endothelium-dependent vasodilatation of the mesenteric arterial bed seen in STZ-induced diabetic rats may be largely due to a defective vascular response to EDHF. It is further suggested that K + is one of the endothelium-derived hyperpolarizing factors and that the vasodilatation response to K + is impaired in the mesenteric arterial bed from diabetic rats.
KW - Diabetes
KW - Endothelium
KW - Endothelium-derived hyperpolarizing factor
KW - Mesenteric arterial bed
KW - Rat
KW - Streptozotocin
UR - http://www.scopus.com/inward/record.url?scp=0034073160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034073160&partnerID=8YFLogxK
M3 - Article
VL - 130
SP - 549
EP - 556
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 3
ER -