Recovery of impaired K+ channels in mesenteric arteries from spontaneously hypertensive rats by prolonged treatment with cholecalciferol

被引:48
作者
Borges, ACR [1 ]
Feres, T [1 ]
Vianna, LM [1 ]
Paiva, TB [1 ]
机构
[1] Escola Paulista Med, Dept Biophys, BR-04023062 Sao Paulo, Brazil
关键词
SHR; mesenteric arteries; cholecalciferol; membrane potential; alpha-2; adrenoceptors; K+ channels;
D O I
10.1038/sj.bjp.0702581
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The mechanism responsible for blood pressure reduction in spontaneously hypertensive rats (SHR) after prolonged cholecalciferol treatment was studied. Two-week treatment of SHR with 0.125 mg cholecalciferol kg(-1) body weight per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at constant flow. 2 In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca2+-dependent K+ channels coupled to alpha(2)-adrenoceptors since it was prevented by apamin. 3 The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and their hyperpolarizing responses to alpha(2)-adrenergic agonists, which were depressed in untreated SHR. 4 In mesenteric rings with endothelium, alpha(2)-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (NWR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while in NWR it was the endothelium-derived hyperpolarizing factor (EDI-IF). After cholecalciferol treatment, the hyperpolarization induced by alpha(2)-adrenergic agonists in SHR smooth muscle cells was mediated by EDHF, as in NWR. 5 Our results indicate that the hypotensive effect of cholecalciferol in the SHR is probably due to the normalization of vascular reactivity, by restoring the functioning of apamin- and ATP-sensitive K+ channels located in the vascular smooth muscle cell membrane, which are impaired in the SHR.
引用
收藏
页码:772 / 778
页数:7
相关论文
共 31 条
[1]   INCREASED DIETARY CALCIUM LOWERS BLOOD-PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
AYACHI, S .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1979, 28 (12) :1234-1238
[2]   REGULATION OF ARTERIAL TONE BY ACTIVATION OF CALCIUM-DEPENDENT POTASSIUM CHANNELS [J].
BRAYDEN, JE ;
NELSON, MT .
SCIENCE, 1992, 256 (5056) :532-535
[3]   EFFECT OF LONG-TERM ADMINISTRATION OF 125 (OH)2 VITAMIN-D(3) ON BLOOD-PRESSURE AND RESISTANCE ARTERY CONTRACTILITY IN THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
BUKOSKI, RD ;
LI, JY ;
BO, J .
AMERICAN JOURNAL OF HYPERTENSION, 1993, 6 (11) :944-950
[4]   INJECTION OF 1,25-(OH)2 VITAMIN-D3 ENHANCES RESISTANCE ARTERY CONTRACTILE PROPERTIES [J].
BUKOSKI, RD ;
WANG, D ;
WAGMAN, DW .
HYPERTENSION, 1990, 16 (05) :523-531
[5]   EFFECT OF 1,25(OH)2 VITAMIN-D3 AND IONIZED CA-2+ ON CA-45 UPTAKE BY PRIMARY CULTURES OF AORTIC MYOCYTES OF SPONTANEOUSLY HYPERTENSIVE AND WISTAR KYOTO NORMOTENSIVE RATS [J].
BUKOSKI, RD ;
HONG, X ;
MCCARRON, DA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 146 (03) :1330-1335
[6]   MESENTERIC ARCADE ARTERIES CONTRIBUTE SUBSTANTIALLY TO VASCULAR-RESISTANCE IN CONSCIOUS RATS [J].
CHRISTENSEN, KL ;
MULVANY, MJ .
JOURNAL OF VASCULAR RESEARCH, 1993, 30 (02) :73-79
[7]   EFFECT OF TREATMENT WITH VITAMIN-D3 ON THE RESPONSES OF THE DUODENUM OF SPONTANEOUSLY HYPERTENSIVE RATS TO BRADYKININ AND TO POTASSIUM [J].
FERES, T ;
VIANNA, LM ;
PAIVA, ACM ;
PAIVA, TB .
BRITISH JOURNAL OF PHARMACOLOGY, 1992, 105 (04) :881-884
[8]   Impaired function of alpha-2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats [J].
Feres, T ;
Borges, ACR ;
Silva, EG ;
Paiva, ACM ;
Paiva, TB .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 125 (06) :1144-1149
[9]   DECREASED ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION TO ACETYLCHOLINE IN SMOOTH-MUSCLE OF THE MESENTERIC-ARTERY OF SPONTANEOUSLY HYPERTENSIVE RATS [J].
FUJII, K ;
TOMINAGA, M ;
OHMORI, S ;
KOBAYASHI, K ;
KOGA, T ;
TAKATA, Y ;
FUJISHIMA, M .
CIRCULATION RESEARCH, 1992, 70 (04) :660-669
[10]   RESPONSE OF SPONTANEOUSLY HYPERTENSIVE RATS TO 1,25(OH)2D3 INVIVO [J].
GAFTER, U ;
EBY, B ;
MARTIN, C ;
LAU, K .
KIDNEY INTERNATIONAL, 1986, 30 (04) :497-502