The effect of diabetes and sex on nitric oxide-mediated cardiovascular dynamics

Diabetes is associated with impaired cardiovascular responses that are espe cially prominent in females. Since nitric oxide (NO)-mediated effects on ca rdiovascular dynamics are altered in diabetes, we evaluated the effect of L -NAME, a nitric oxide synthase (NOS) antagonist, on mean arterial pressure (MAP), heart rate (HR), and selective vascular flows in both male and femal e normal and diabetic rats as an index of NO activity. Rats were made diabe tic using streptozotocin and maintained for 5-6 weeks. Following anesthesia with urethane/alpha -chloralose, the femoral artery and vein were cannulat ed for recording and sampling, and flow probes were placed on the iliac, re nal, and superior mesenteric arteries. A bolus infusion of L-NAME (10mg/kg) resulted in a rapid +52% and + 68% increase in MAP in normal female and ma le rats, respectively, However, diabetic females' and males' responses were significantly lower (44% and 45%, respectively) when compared with their n ormal counterparts. The decreased HR in response to the peak presser effect of L-NAME was more prominent in normal females compared with normal males (-14% vs 2%). The results in diabetic females and males were equivalent (-6 % vs -9%, respectively). L-NAME decreased the conductance (flow/MAP) an ave rage of 65% in all three vascular beds in normal female rats. In diabetic f emales, the iliac and superior mesenteric responses to L-NAME were less, an d the renal conductance was contrastingly increased 23%. The response to L- NAME was comparable (-62%) in the renal and superior mesenteric and less (- 40%) in the iliacs of normal versus diabetic males. We concluded that diabe tes is associated with a decreased presser response to NOS inhibition. And the impaired constriction response of the renal vessels noted in female dia betic rats may provide a basis for the increased renal pathology observed i n diabetic humans.