Vascular KATP channel blockade by glibenclamide, but not by acarbose, in patients with Type II diabetes

2002 ◽  
Vol 102 (3) ◽  
pp. 307-314
Author(s):  
E.J. ABBINK ◽  
P. PICKKERS ◽  
A. Jansen VAN ROSENDAAL ◽  
J.A. LUTTERMAN ◽  
C.J. TACK ◽  
...  
Keyword(s):  
Blood Flow ◽  
Type Ii Diabetes ◽  
Katp Channel ◽  
Forearm Blood Flow ◽  
Cardiovascular Effects ◽  
Venous Occlusion ◽  
Type Ii Diabetes Mellitus ◽  
Protective Mechanism ◽  
Type Ii ◽  
Double Blind

Glibenclamide inhibits the opening of vascular ATP-sensitive potassium (KATP) channels, which represents a protective mechanism during ischaemia. This effect may imply harmful cardiovascular effects of glibenclamide when used under conditions of ischaemia in patients with Type II diabetes. Acarbose is not associated with effects on the cardiovascular system, because the drug is not absorbed from the bowel. Therefore we hypothesized that treatment of Type II diabetes patients with glibenclamide will impair the vasodilator function of KATP opening, unlike treatment with acarbose. A double-blind randomized cross-over study in 12 patients with Type II diabetes was performed to compare the effects of glibenclamide with those of acarbose on the vasodilator responses to KATP channel opening in the forearm vascular bed. The study consisted of two periods: 8 weeks of treatment with orally administered glibenclamide (10mgċday-1) followed by 8 weeks of treatment with acarbose (300mgċday-1), or vice versa. At the end of each treatment period, forearm blood flow (venous occlusion plethysmography) in response to intra-arterially administered diazoxide, acetylcholine and dipyridamole and to forearm ischaemia was measured. The diazoxide-mediated increase in the forearm blood flow ratio (infused/control arm) was significantly less pronounced after glibenclamide than after acarbose (290±58% and 561±101% respectively; P < 0.0005). Forearm blood flow responses to acetylcholine, dipyridamole and forearm ischaemia were similar during glibenclamide and acarbose treatment. Thus, in patients with Type II diabetes mellitus, treatment with glibenclamide is associated with an attenuated response to KATP opening as compared with treatment with acarbose. This implies that glibenclamide may affect defensive mechanisms under conditions of KATP channel activation.

scholarly journals The influence of plasma glucose upon pulsatile ocular blood flow in subjects with Type II diabetes mellitus

Diabetologia ◽  
2001 ◽  
Vol 44 (6) ◽  
pp. 700-705 ◽  
Author(s):  
R. L. Perrott ◽  
R. V. North ◽  
N. Drasdo ◽  
K. A. Ahmed ◽  
D. R. Owens
Keyword(s):  
Diabetes Mellitus ◽  
Blood Flow ◽  
Plasma Glucose ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Ocular Blood Flow ◽  
Type Ii ◽  
Pulsatile Ocular Blood Flow

scholarly journals Activation of ATP-sensitive potassium channels contributes to reactive hyperemia in humans

1996 ◽  
Vol 271 (4) ◽  
pp. H1594-H1598 ◽  
Author(s):  
P. F. Banitt ◽  
P. Smits ◽  
S. B. Williams ◽  
P. Ganz ◽  
M. A. Creager
Keyword(s):  
Blood Flow ◽  
Katp Channel ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Katp Channels ◽  
Venous Occlusion ◽  
Membrane Hyperpolarization ◽  
Flow Response ◽  
Hyperemic Flow ◽  
Basal Flow

Activation of ATP-sensitive potassium (KATP) channels present on vascular smooth muscle cells causes membrane hyperpolarization and vasodilation. The purpose of this study was to determine whether KATP channels contribute to reactive hyperemia in humans. Accordingly, we studied the effect of tolbutamide, a KATP channel inhibitor, on reactive hyperemic forearm blood flow. Forearm blood flow was measured by venous occlusion plethysmography. Forearm ischemia was produced by inflating a sphygmomanometric cuff on the arm to suprasystolic pressures for 5 min. After cuff release, forearm blood flow was measured during the reactive hyperemic phase for 5 min. Tolbutamide (1 mM blood concentration, n = 6) did not affect basal (2.4 +/- 0.2 to 2.2 +/- 0.1 ml.100 ml-1.min-1) or peak reactive hyperemic forearm blood flow (21.9 +/- 3.8 to 22.6 +/- 2.9 ml.100 ml-1.min-1, each P = NS), but it significantly attenuated total hyperemic volume (12.6 +/- 1.7 vs. 9.2 +/- 1.8 ml/100 ml, P < 0.02). Vehicle (n = 6) did not affect basal flow, peak reactive hyperemic flow, or total hyperemia. To determine whether adenosine or endothelium-derived nitric oxide contribute to reactive hyperemia via KATP channels, adenosine (1.5-500 micro grams/min, n = 6) and acetylcholine (30 micrograms/min, n = 6) were infused before and during tolbutamide coinfusion. Tolbutamide did not significantly alter the forearm blood flow response to either adenosine or acetylcholine. In conclusion, KATP channels contribute to vasodilation during reactive hyperemia in humans.

Lack of effect of oral vitamin C on blood pressure, oxidative stress and endothelial function in Type II diabetes

2002 ◽  
Vol 103 (4) ◽  
pp. 339-344 ◽  
Author(s):  
D. DARKO ◽  
A. DORNHORST ◽  
F.J. KELLY ◽  
J.M. RITTER ◽  
P.J. CHOWIENCZYK
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Blood Flow ◽  
Vitamin C ◽  
Endothelial Function ◽  
Type Ii Diabetes ◽  
Forearm Blood Flow ◽  
Plasma Concentrations ◽  
Type Ii ◽  
Oral Vitamin

Type II diabetes is characterized by increased oxidative stress, endothelial dysfunction and hypertension. We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes. Subjects (n = 35) received vitamin C (1.5g daily in three doses) or matching placebo for 3 weeks in a randomized, double-blind, parallel-group design. Plasma concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α), a non-enzymically derived oxidation product of arachidonic acid, were used as a marker of oxidative stress. Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine (with nitroprusside as an endothelium-independent control) and by the pulse wave responses to systemic albuterol (endothelium-dependent vasodilator) and glyceryl trinitrate (endothelium-independent vasodilator). Plasma concentrations of vitamin C increased from 58±6 to 122±10μmol/l after vitamin C, but 8-epi-PGF2α levels (baseline, 95±4pg/l; after treatment, 99±5pg/l), blood pressure (baseline, 141±5/80±2mmHg; after treatment, 141±5/81±3mmHg) and endothelial function, as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine, were not significantly different from baseline or placebo. Thus treatment with vitamin C (1.5 g daily) for 3 weeks does not significantly improve oxidative stress, blood pressure or endothelial function in patients with Type II diabetes.

Hypercapnia-induced cerebral and ocular vasodilation is not altered by glibenclamide in humans

2000 ◽  
Vol 278 (6) ◽  
pp. R1667-R1673 ◽  
Author(s):  
Michaela Bayerle-Eder ◽  
Michael Wolzt ◽  
Elzbieta Polska ◽  
Herbert Langenberger ◽  
Johannes Pleiner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Crossover Study ◽  
Flow Velocity ◽  
Forearm Blood Flow ◽  
Resistive Index ◽  
Venous Occlusion ◽  
Mean Flow ◽  
Choroidal Blood Flow ◽  
Double Blind ◽  
Induced Changes

Carbon dioxide is an important regulator of vascular tone. Glibenclamide, an inhibitor of ATP-sensitive potassium channel (KATP) activation, significantly blunts vasodilation in response to hypercapnic acidosis in animals. We investigated whether glibenclamide also alters the cerebral and ocular vasodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a controlled, randomized, double-blind two-way crossover study under normoxic and hypercapnic conditions. Glibenclamide (5 mg po) or insulin (0.3 mU ⋅ kg− 1 ⋅ min− 1iv) were administered with glucose to achieve comparable plasma insulin levels. In control experiments, five healthy volunteers received glibenclamide (5 mg) or nicorandil (40 mg) or glibenclamide and nicorandil in a randomized, three-way crossover study. Mean blood flow velocity and resistive index in the middle cerebral artery (MCA) and in the ophthalmic artery (OA) were measured with Doppler sonography. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. Forearm blood flow was measured with venous occlusion plethysmography. Hypercapnia increased ocular fundus pulsation amplitude by +18.2–22.3% ( P < 0.001) and mean flow velocity in the MCA by +27.4–33.3% ( P < 0.001), but not in the OA (2.1–6.5%, P = 0.2). Forearm blood flow increased by 78.2% vs. baseline ( P = 0.041) after nicorandil administration. Glibenclamide did not alter hypercapnia-induced changes in cerebral or ocular hemodynamics and did not affect systemic hemodynamics or forearm blood flow but significantly increased glucose utilization and blunted the nicorandil-induced vasodilation in the forearm. This suggests that hypercapnia-induced changes in the vascular beds under study are not mediated by activation of KATPchannels in humans.

Cardiovascular Effects of Marihuana in Man

1974 ◽  
Vol 52 (3) ◽  
pp. 706-719 ◽  
Author(s):  
S. C. Clark ◽  
C. Greene ◽  
G. W. Karr ◽  
K. L. MacCannell ◽  
S. L. Milstein
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Physiological Responses ◽  
Vagal Tone ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Venous Compliance ◽  
Double Blind ◽  
Arterial Resistance

Twenty-eight subjects, matched by sex and Cannabis experience, received by controlled inhalation under single- and double-blind conditions 600 mg marihuana placebo and marihuana. Forearm, venous and arterial pressures, forearm blood flow, and heart rate were recorded while supine. Derived functions such as "dp/dt", regional arterial resistance, and venous compliance were calculated from these variables. (1) Placebo produced no intoxication or consistent physiological responses. (2) Marihuana produced intoxication in all Cannabis-experienced and half the non-experienced subjects. (3) Cardiovascular responses occurred in response to marihuana in the absence of intoxication, indicating that they were not psychogenically mediated. (4) Inhibition of vagal tone may contribute to the tachycardia seen with marihuana. (5) Reflexly mediated sympathetic responses may be muted in the presence of marihuana.

scholarly journals Silymarin, Olibanum, and Nettle, A Mixed Herbal Formulation in the Treatment of Type II Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial

2017 ◽  
Vol 22 (4) ◽  
pp. 603-608 ◽  
Author(s):  
Nahid Khalili ◽  
Reza Fereydoonzadeh ◽  
Reza Mohtashami ◽  
Saeed Mehrzadi ◽  
Mojtaba Heydari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trial ◽  
Type Ii Diabetes ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Type Ii Diabetes Mellitus ◽  
Controlled Clinical Trial ◽  
Type Ii ◽  
Double Blind ◽  
Herbal Formulation

Silybum marianum (L) Gaertn (milk thistle) seeds, Urtica dioica L (nettle) leaves, and Boswellia serrata (olibanum gum) resin are used traditionally by Iranian diabetic patients. The aim of this study was to evaluate the antihyperglycemic effects of these herbs in an herbal formulation in patients with type II diabetes mellitus. Sixty patients diagnosed as type II diabetes mellitus with fasting blood glucose level from 150 to 180 mg/dL, glycosylated hemoglobin level from 7.5% to 8.5%, and on oral antihyperglycemic drugs, were allocated to receive the mix herbal formulation or placebo for 90 days in a double-blind randomized placebo-controlled clinical trial. The mean serum fasting blood glucose, glycosylated hemoglobin, and triglyceride in the herbal drug group were significantly less than placebo group’s values after 3 months of the intervention. The study showed a potential antihyperglycemic and triglyceride lowering effect of the herbal formulation, while it did not have any significant cholesterol or blood pressure lowering effect.

Impact Of Caffeine On Exercising Forearm Blood Flow And VO2 In Type II Diabetes

2010 ◽  
Vol 42 ◽  
pp. 242
Author(s):  
Veronica Poitras ◽  
Michael Bravo ◽  
Melissa Pak ◽  
Michael E. Tschakovsky
Keyword(s):  
Blood Flow ◽  
Type Ii Diabetes ◽  
Forearm Blood Flow ◽  
Type Ii

scholarly journals Effects of 1 MHz Therapeutic Ultrasound on Limb Blood Flow and Microvascular Reactivity: A Randomized Pilot Trial

2021 ◽  
Vol 18 (21) ◽  
pp. 11444
Author(s):  
Megan Waters ◽  
Branko Miljkovic ◽  
Jozelyn Rascon ◽  
Manuel Gomez ◽  
Alvaro N. Gurovich
Keyword(s):  
Blood Flow ◽  
Repeated Measures ◽  
Forearm Blood Flow ◽  
Pilot Trial ◽  
Therapeutic Ultrasound ◽  
Venous Occlusion ◽  
Double Blind ◽  
Effective Treatment Modality ◽  
Group Time ◽  
Before And After

A randomized, double-blind, placebo-controlled, cross-over study where continuous therapeutic ultrasound (CUS; at 0.4 W/cm2), pulsed therapeutic ultrasound (PUS; at 20% duty cycle, 0.08 W/cm2), both at 1 MHz, and placebo (equipment on, no energy provided) were randomized and applied over the forearm of the non-dominant arm for 5 min in 10 young, healthy individuals. Absolute and peak forearm blood flow (FBF) were measured via Venous Occlusion Plethysmography. FBF was measured before, halfway, and after (immediately and 5 min after) the therapeutic ultrasound (TUS) intervention. Post-ischemic peak FBF was measured 10 min before and 10 min after the TUS intervention. A two-way repeated measures ANOVA (group × time) was selected to assess differences in FBF before, during, and after TUS treatment, and for peak FBF before and after TUS treatment. FBF increased 5 min after TUS in CUS compared to placebo (2.96 ± 1.04 vs. 2.09 ± 0.63 mL/min/100 mL of tissue, p < 0.05). PUS resulted in the greatest increase in Peak FBF at 10 min after US (Δ = 3.96 ± 2.02 mL/min/100 mL of tissue, p = 0.06). CUS at 1 MHz was an effective treatment modality for increasing FBF up to 5 min after intervention, but PUS resulted in the greatest increase in peak FBF at 10 min after intervention.

Sign in / Sign up

Export Citation Format

Share Document