Obesity and hyperinsulinism are known to be major stimuli of leptin production by adipose tissue, leading to increased leptin levels in the circulation. It has also been demonstrated that increased leptin production leads to satiety, possibly by decreasing the levels of neuropeptide Y (NPY) in the central nervous system (CNS). Because obesity and hyperinsulinism are also frequently associated with hypertension, we studied the effect of the intracerebroventricular (ICV) administration of leptin on mean arterial pressure (MAP), heart rate, vascular flows, and lumbar and renal sympathetic nerve activity (SNA). Normal Wistar rats were implanted with an ICV cannula and allowed to recover. On the day of the study, the animals were fasted and anesthetized with chloralose/urethane. Catheters were placed in a femoral artery and vein, and Doppler flow probes were placed around the iliac, renal, and superior mesenteric arteries for measurement of MAP, heart rate, and blood flows. In other experiments, lumbar SNA and renal SNA were recorded. ICV leptin administration resulted in an MAP that was slowly but progressively increasing. Blood flows decreased in the iliac and superior mesenteric arteries, but not in the renal artery. Leptin injection increased the lumbar SNA and renal SNA. The plasma glucose and insulin levels were not changed. We concluded that ICV leptin increases MAP by decreasing arterial blood flow to the skeletal muscle and the splanchnic vascular bed. This increased peripheral resistance is the result of an increased activity of the sympathetic nerves. We suggest that increased leptin may serve as a link in the triad of obesity and hyperinsulinism and hypertension.
The insulin-like growth factor-I (IGF-I) and its receptors are widely distributed in peripheral vascular tissue, yet their role in the regulation of blood pressure and blood flow remains unknown. This study investigated the effect of IGF-I on blood pressure and selected regional blood flow in normal Wistar rats anesthetized with chloralose/urethane. The femoral artery was cannulated and used to monitor arterial blood pressure. Electromagnetic flow probes were placed around the left common iliac artery, left renal artery, and the superior mesenteric artery, and used to measure blood flow. IGF-I (2.6 micrograms, 5.1 or 10.3 nmol/animal Iv) was injected as a bolus into the femoral vein. Following the injection of IGF-I (10.3 nmol), we observed a significant decrease of plasma glucose (57%) and a significant decrease of mean arterial pressure (MAP) that continued to decline throughout the 60-min experimental period. IGF-I (5.1 nmol) significantly decreased blood glucose by 44% and decreased the MAP by 14% with a nadir at 15 min and recovery after 60 min. A smaller dose of IGF-I (2.6 nmol) did not significantly decrease the blood glucose but resulted in a slight but significant decrease in MAP. The heart rate was increased by 10.3 and 5.1 but not 2.5 nmol of IGF-I. IGF-I (10.3 nmol) was associated with regional vascular responses with a preferential increase in flow of the iliac and superior mesenteric vessels, measured as vascular conductance. IGF-I (5.1 and 2.6 nmol) increased preferentially renal vascular conductance. Preinfusion with L-NAME, a nitric oxide inhibitor, inhibited the effects of IGF-I on flow. We conclude that IGF-I can selectively dilate vascular beds leading to a decrease in blood pressure and that the response to IGF-I is mediated by nitric oxide.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.