Abstract
Vascular disease has importance in chronic diabetes mellitus but long-term impact
of maternal diabetes (MD) on vascular function in the offspring is poorly investigated.
This study aimed to examine the alterations produced by MD in K+ channels activity on endothelium-dependent aortic relaxation induced by acetylcholine
(ACh) in adult offspring rats. Diabetes mellitus was induced in female Wistar rats
by streptozotocin (STZ; 42 mg/kg, i. p.) injected on the 7th day of pregnancy. Body weights of offspring rats from diabetic mothers (O-DR) were
significantly lesser than those of offspring rats from control mothers (O-CR). At
120 days of age, triglyceride but not glucose and cholesterol level was significantly
higher in O-DR than in O-CR. In aortic preparations from O-DR, norepinephrine (NE)-induced
contractions were significantly higher than those observed in O-CR. In aortic preparations
from O-DR precontracted with NE (1 μM), vasorelaxant response to either ACh (0.1,
1 and 10 μM) or sodium nitroprusside (0.1, 1 and 10 nM) was significantly reduced
when compared to O-CR. In both groups, vasorelaxant responses to ACh were reduced
in the presence of tetraethylamonium chloride and 4-aminopyridine. However, pretreatment
with glybenclamide reduced vasorelaxant effects of lowest concentration (0.1 μM) of
ACh only in preparations from O-CR. Our results suggest a reduced K+
ATP activity in the cholinergic relaxation of aortic rings of adult offspring born to
STZ-diabetic mothers.
Key words
acetylcholine - aorta relaxation - K+
ATP channels - maternal diabetes - offspring
References
- 1
Aerts L, Holemans K, Van Assche FA.
Maternal diabetes during pregnancy: consequences for the offspring.
Diabetes Metab Rev.
1990;
6
147-167
- 2
Aerts L, Vercruysse L, Van Assche FA.
The endocrine pancreas in virgin and pregnant offspring of diabetic pregnant rats.
Diabetes Res Clin Pract.
1997;
38
9-19
- 3
Cook NS.
Effect of some potassium channel blockers on contractile responses of the rabbit aorta.
J Cardiovasc Pharmacol.
1989;
13
299-306
- 4
Félétou M, Vanhoutte PM.
Endothelium-derived hyperpolarizing factor: where are we now? Arterioscler.
Thromb Vasc Biol.
2006;
26
1215-1225
- 5
Han J, Xu J, Long YS. et al .
Rat maternal diabetes impairs pancreatic beta-cell function in the offspring.
Am J Physiol Endocrinol Metab.
2007;
293
E228-E236
- 6
Holemans K, Gerber RT, Meurrens K. et al .
Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in
adult offspring.
Diabetologia.
1999;
42
81-89
- 7
Koukkou E, Ghosh P, Lowy C. et al .
Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular
dysfunction.
Circulation.
1998;
98
2899-2904
- 8
López-Soldado I, Herrera E.
Different diabetogenic response to moderate doses of streptozotocin in pregnant rats,
and its long-term consequences in the offspring.
Experimental Diab Res.
2003;
4
107-118
- 9
Ryan EA, Liu D, Bell RC. et al .
Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic
islet-transplanted streptozotocin-diabetic rats.
Endocrinology.
1995;
136
5587-5592
- 10
Salbe AD, Lindsay RS, Collins CB. et al .
Comparison of plasma insulin levels after a mixed-meal challenge in children with
and without intrauterine exposure to diabetes.
J. Clin Endocrinol Metab.
2007;
92
624-628
- 11
Satake N, Shibata M, Shibata S.
The inhibitory effects of iberiotoxin and 4-aminopyridine on the relaxation induced
by beta1- and beta2-adrenoceptor activation in rat aortic rings.
Br J Pharmacol.
1996;
119
505-510
- 12
Segar EM, Norris AW, Yao JR. et al .
Programming of growth, insulin resistance and vascular dysfunction in offspring of
late gestation diabetic rats.
Clin Sci Lond.
2009;
117
129-138
- 13
Standen NB, Quayle JM, Davies NW. et al .
Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth
muscle.
Science.
1989);
245
177-180
- 14
Wichi RB, Souza SB, Casarini DE. et al .
Increased blood pressure in the offspring of diabetic mothers.
Am J Physiol Regul Integr Comp Physiol.
2005);
288
R1129-R1133
Correspondence
Dr. P. J. C. Magalhães
Departamento de Fisiologia
e Farmacologia
R. Cel Nunes de Melo 1127
Fortaleza
CE
Brazil
Phone: (+55) 85 3366 8334
Fax: (+55) 85 3366 8334
Email: pjcmagal@ufc.br
