Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo

被引:664
作者
Williams, SB
Goldfine, AB
Timimi, FK
Ting, HH
Roddy, MA
Simonson, DC
Creager, MA
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrine, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA
关键词
diabetes mellitus; endothelium-derived factors; vasodilation; glucose; nitric oxide;
D O I
10.1161/01.CIR.97.17.1695
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Endothelial function is impaired in patients with diabetes mellitus, However, the factors contributing to this defect are currently unknown. Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit arteries in vitro and rat arterioles in vivo. Accordingly, this study examined the effect of acute hyperglycemia on endothelium-dependent vasodilation in nondiabetic humans in vivo. Methods and Results-Endothelium-dependent vasodilation was assessed through brachial artery infusion of methacholine chloride both before and during 6 hours of local hyperglycemia (300 mg/dL) achieved by intra-arterial infusion of 50% dextrose, Forearm blood flow was determined by plethysmography, In a group of 10 subjects, there was a trend toward attenuated methacholine-mediated vasodilation during hyperglycemia compared with euglycemia (P=.07 by ANOVA; maximal response, 13.3+/-2.8 versus 14.7+/-1.5 mL . min(-1). 100 mL(-1), respectively). In these subjects, the systemic serum insulin levels increased significantly during the dextrose infusion (P<.001), To eliminate the confounding vasoactive effects of insulin, the protocol was repeated during systemic infusion of octreotide (30 ng . kg(-1). min(-1)) to inhibit pancreatic secretion of insulin. In these subjects (n=10), hyperglycemia significantly attenuated the forearm blood flow response to methacholine (P<.01 by ANOVA; maximal response, 16.9+/-2.5 before versus 12.7+/-1.8 mL . min(-1). 100 mL(-1) during hyperglycemia). Methacholine-mediated vasodilation was not attenuated by an equimolar infusion of mannitol (P>.40), nor did hyperglycemia reduce endothelium-independent vasodilation to verapamil (P>.50), Conclusions-Acute hyperglycemia impairs endothelium-dependent vasodilation in healthy humans in vivo. This finding suggests that elevated glucose may contribute to the endothelial dysfunction observed in patients with diabetes mellitus.
引用
收藏
页码:1695 / 1701
页数:7
相关论文
共 55 条
[1]   HYPERINSULINEMIA PRODUCES BOTH SYMPATHETIC NEURAL ACTIVATION AND VASODILATION IN NORMAL HUMANS [J].
ANDERSON, EA ;
HOFFMAN, RP ;
BALON, TW ;
SINKEY, CA ;
MARK, AL .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (06) :2246-2252
[2]   PERIPHERAL ARTERIAL-DISEASE IN RELATION TO GLYCEMIC LEVEL IN AN ELDERLY CAUCASIAN POPULATION - THE HOORN STUDY [J].
BEKS, PJ ;
MACKAAY, AJC ;
DENEELING, JND ;
DEVRIES, H ;
BOUTER, LM ;
HEINE, RJ .
DIABETOLOGIA, 1995, 38 (01) :86-96
[3]   TOPICAL HYPERGLYCEMIA RAPIDLY SUPPRESSES EDRF-MEDIATED VASODILATION OF NORMAL RAT ARTERIOLES [J].
BOHLEN, HG ;
LASH, JM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (01) :H219-H225
[4]  
BREDT DS, 1992, J BIOL CHEM, V267, P10976
[5]   ELEVATED GLUCOSE ALTERS EICOSANOID RELEASE FROM PORCINE AORTIC ENDOTHELIAL-CELLS [J].
BROWN, ML ;
JAKUBOWSKI, JA ;
LEVENTIS, LL ;
DEYKIN, D .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (06) :2136-2141
[6]   ADVANCED GLYCOSYLATION PRODUCTS QUENCH NITRIC-OXIDE AND MEDIATE DEFECTIVE ENDOTHELIUM-DEPENDENT VASODILATATION IN EXPERIMENTAL DIABETES [J].
BUCALA, R ;
TRACEY, KJ ;
CERAMI, A .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (02) :432-438
[7]   INHIBITION AND STIMULATION OF NITRIC-OXIDE SYNTHESIS IN THE HUMAN FOREARM ARTERIAL BED OF PATIENTS WITH INSULIN-DEPENDENT DIABETES [J].
CALVER, A ;
COLLIER, J ;
VALLANCE, P .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (06) :2548-2554
[8]  
CREAGER MA, 1985, J PHARMACOL EXP THER, V235, P709
[9]   INHIBITION OF NITRIC-OXIDE SYNTHESIS IN FOREARM VASCULATURE OF INSULIN-DEPENDENT DIABETIC-PATIENTS - BLUNTED VASOCONSTRICTION IN PATIENTS WITH MICROALBUMINURIA [J].
ELLIOTT, TG ;
COCKCROFT, JR ;
GROOP, PH ;
VIBERTI, GC ;
RITTER, JM .
CLINICAL SCIENCE, 1993, 85 (06) :687-693
[10]   NITRIC OXIDE-GENERATING VASODILATORS AND 8-BROMO-CYCLIC GUANOSINE-MONOPHOSPHATE INHIBIT MITOGENESIS AND PROLIFERATION OF CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
GARG, UC ;
HASSID, A .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) :1774-1777