Nicotine effects on renal function in experimental diabetes
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Smoking has been recognized as a major risk factor for the development and progression of kidney disease in patients with both insulin dependent and non insulin dependent diabetes mellitus. As a risk factor, smoking 1) increases the risk for the presence of protein in the urine, 2) shortens the time interval between onset of diabetes and onset of presence of protein in the urine, and 3) accelerates the rate at which patients lose kidney function and require dialysis in order to live. In spite of the major impact of smoking in progression of diabetic renal disease, very little is known about the mechanism(s) by which smoking accelerates renal injury. Preliminary studies obtained for this submission demonstrate that intravenous administration of nicotine (as a surrogate for smoking) increases hydrostatic pressure in the kidney filtering unit (glomerulus). This increase in glomerular hydrostatic pressure has been recognized as a major risk factor for the progression of kidney disease in experimental model of diabetes. Since glomerular hypertension is such an important risk factor, this proposal will focus in defining the mechanism(s) by which nicotine increases glomerular pressure. Studies will be directed at analyzing the role of various hormones or mediators including angiotensin II, nitric oxide and renal nerves.
 
 
 
 
 
 In Specific Aim #1 of this project we will investigate if increased levels of angiotensin II (a major hormone in the kidney) are responsible for the increase in glomerular pressure during nicotine administration. These studies will include measurements of kidney angiotensin II after nicotine administration and studies examining the effects of drugs capable of suppressing angiotensin II generation.
 
 
 
 
 
 Previous studies in humans and experimental animals have demonstrated that nicotine suppresses the production of an important vasodilator, nitric oxide. In Specific Aim # 2 we will test the hypothesis that nicotine induced glomerular hypertension is secondary to decreased production of nitric oxide. Studies will include measurements of nitric oxide and test examining the capacity of nicotine treated kidneys to respond to agents capable of directly stimulating nitric oxide production.
 
 
 
 
 
 Nicotine is also known to induce increased adrenergic activity. In Specific Aim #3 we will investigate the role of increased sympathetic activity as a mechanism responsible for increasing angiotensin II activity. These studies will examine the effects of surgical section of the renal nerves (renal denervation) and administration of agents capable of blocking the effects of renal nerves on the renal response to nicotine administration.
 
 
 
 
 
 The long term goal of this project is to define the mechanism(s) responsible for nicotine induced renal injury and utilize this knowledge to develop specific treatments capable of preventing the deleterious effects of nicotine on progression of kidney disease in smokers.