Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats.
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.
Dunbar
J C
JC
Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA. jdunbar@med.wayne.edu
Hu
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D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000294:innervation*; D007700:Kinetics; D020738:Leptin; D008159:Lumbar Vertebrae / Q000294:innervation; D008297:Male; D011506:Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011506:Proteins