Vascular dilatatory responses to sodium nitroprusside (SNP) and alpha-adrenergic antagonism in female and male normal and diabetic rats.
Diabetes is associated with impaired vascular dilatatory responses that appear to be influenced by sex as well as diabetic state. Therefore, we hypothesized that vascular and sympathetic control function exhibit a greater deterioration following the induction of diabetes in female than in male rats. We conducted a comparative determination of the effect of sodium nitroprusside (SNP, a nitrous oxide donor) and that of an alpha1-adrenergic antagonist, prazosin, on selective vascular flows, mean arterial pressure (MAP), and heart rate (HR), in female and male normal and diabetic rats. Rats were made diabetic using streptozotocin (50 mg/kg, iv) and maintained for 5-6 weeks. Following anesthesia with urethane/alpha-chloralose, the femoral artery and vein were cannulated for recording and sampling. Flow probes were placed on the iliac, renal, and superior mesenteric arteries. SNP (1, 5, 10, and 20 microg/kg) infusions resulted in a dose-dependent decrease in MAP in normal and diabetic rats. The decrease in MAP in normal males was 37% less at the 20 microg/kg concentration of SNP when compared to normal females. The HR was not significantly changed in response to the hypotensive effect of SNP; however, reflex tachycardia was more prominent in diabetic males. The vascular conductance (flow/MAP) was increased by SNP in normal and diabetic rats in a dose-dependent fashion; however, the responsiveness was decreased in the iliac and superior mesenteric and increased in the renal arteries in diabetics when compared to normals. Diabetic males were 42% and 28% less responsive to SNP in the iliac and superior mesenteric arteries, respectively. On the other hand, diabetic females were 1.5-fold more responsive in the renal artery when compared to normals. Prazosin (4 mg/kg) decreased the MAP in normal and diabetic rats to a comparable degree. Prazosin increased the vascular conductance in all three vascular beds in normal and diabetic rats with the greater increase occurring in the iliac (118%) and superior mesenteric (110%) arteries. We concluded that diabetes is associated with an increased response to NO in the renal vessels and a decreased response in the iliac and superior mesenteric vessels in both females and males. alpha-Adrenergic tone was greatest in diabetic female and male rats. This study suggests that decreased vascular flow in diabetes is a result of a combination of decreased sensitivity to NO and increased adrenergic tone.
Martínez-Nieves
B
B
Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.
Dunbar
J C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012737:Sex Factors; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D020030:Nitric Oxide Donors; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; D009599:Nitroprusside; D013311:Streptozocin; D011224:Prazosin