Project/Area Number |
05670629
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Nagoya City University |
Principal Investigator |
ASANO Masahisa Nagoya City University, Medical School Lecturer, 医学部, 講師 (10137078)
|
Project Period (FY) |
1993 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
|
Keywords | Arterial smooth muscle / Ca^<2+>-activated K^+ channels / Ca^<2+>-ion / Essential hypertension / Ca^<2+>活性化K^+チャンネル |
Research Abstract |
We have examined the functional role of Ca^<2+>-activated K^+ (K_<Ca>) channels in arterial smooth muscle of spontaneously hypertensive rats (SHR). Charybdotoxin-sensitive K_<Ca> channels were highly activated to regulate the myogenic tone in the resting state of carotid, femoral and mesenteric arteries from 13-week-old SHR.The increased K_<Ca> channel functions in SHR arteries appeared to be secondary to the increased Ca^<2+> influx via L-type voltage-dependent Ca^<2+> channels (VDCCs) in the resting state of these arteries. Similar results were obtained in arteries from SHR at a prehypertensive stage. Therefore, the increased Ca^<2+> influx via L-type VDCCs in the resting state of the SHR arteries exists in the prehypertensive stage and is one aspect of the pathogenesis of hypertension in SHR.The Ca^<2+> influx via L-type VDCCs was also increased in the resting state of dog cerebral arteries, and therefore the myogenic tone was maintained and the K_<Ca> channels were highly activated. The endothelium of rat basilar artery attenuated the contractile response of smooth muscle to serotonin through the release of endothelium-derived hyperpolarizing factor (EDHF), which can activate K_<Ca> channels. This attenuation was smaller in SHR,probably because the inability of endothelium to release EDHF.Since there was an increased basal Ca^<2+> influx and a high activation of K_<Ca> channeles in the resting state of SHR arteries, these changes might influence the arterial relaxant effects of cromakalim, an opener of ATP-sensitive K^+ channels. These results strongly suggest that the activation of arterial K_<Ca> channels acts as a negative feedback mechanism to regulate the level of resting tone and that this activation is important in the SHR arteries but is not enough to abolish the myogenic tone in these arteries.
|