Alpha-lipoic acid treatment prevents the diabetes-induced attenuation of the afferent limb of the baroreceptor reflex in rats.
Autonomic neuropathies, common complications of prolonged diabetes, may result from diabetes-induced increased oxidative stress. Recently, we found that the afferent component of the baroreceptor reflex is attenuated in streptozotocin-induced diabetic rats. This study sought to determine the influence of the anti-oxidant, alpha-lipoic acid on the diabetes-induced deficits of the afferent limb of the baroreceptor reflex and on plasma malondialdehyde (a measure of lipid peroxidation). The number of c-Fos-ir neurons in the nucleus tractus solitarius in response to phenylephrine-induced baroreceptor activation was used as an index of the integrity of the afferent limb of the baroreceptor reflex. Groups of streptozotocin-induced diabetic and non-diabetic control rats, maintained from 8 to 16 weeks, were treated with alpha-lipoic acid (100 mg kg(-1) IP, 5x/week), or vehicle for the last 4 weeks prior to the experimental procedure. Vehicle-treated diabetic rats had elevated plasma malondialdehyde levels when compared to non-diabetic rats. alpha-Lipoic acid-treated diabetic rats had plasma malondialdehyde levels similar to those seen in non-diabetic rats and less than those of vehicle-treated diabetic rats at both the 8- and 16-week time points.alpha-Lipoic acid treatment did not affect the baseline (absence of baroreceptor activation) presence of c-Fos-ir in the nucleus tractus solitarius. In response to phenylephrine and regardless of treatment, the diabetic and control rats displayed increases in blood pressure and reflex bradycardia. As previously reported, phenylephrine-induced baroreceptor activation resulted in significantly fewer c-Fos-ir neurons in the nucleus tractus solitarius (commissural and caudal subpostremal regions) of diabetic rats when compared to non-diabetic rats at both 8- and 16-week time points. Four weeks of alpha-lipoic acid treatment reversed the diabetes-induced decrement in the numbers of c-Fos-ir neurons in the nucleus tractus solitarius in response to baroreceptor activation. alpha-Lipoic acid-treated diabetic rats showed the same phenylephrine-induced c-Fos response in the nucleus tractus solitarius as those of alpha-lipoic-acid- and vehicle-treated control rats at both 8- and 16-week time points. These data suggest that diabetes-induced oxidative stress plays a role in diabetes-induced baroreceptor dysfunction and that the alpha-lipoic acid may have a beneficial effect in treatment of diabetic autonomic neuropathy.
Gouty
Shawn
S
Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. sgouty@usuhs.mil
Regalia
Jen
J
Cai
Fang
F
Helke
Cinda J
CJ
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use*
D008315:Malondialdehyde; D008063:Thioctic Acid