Nicotine Receptors On Kidneys May Speed Kidney Damage

Their research -- presented at the American Heart Association's 60th Annual Fall Conference of the Council for High Blood Pressure Research -- also identifies nicotine as the component of cigarette smoke that damages the kidneys.

"There are many substances in cigarette smoke and nicotine is one of the more investigated ones," said Edgar A. Jaimes, M.D., associate professor of medicine at the University of Miami School of Medicine in Florida. "Initially, it was believed that the nicotine component of cigarette smoke was only responsible for the addictive effects of smoking. However, now we are finding out that nicotine can have significant biological effects in other tissues."

The kidneys regulate the body's excretion and reabsorption of water and electrolytes (sodium, potassium, chloride, calcium, magnesium, sulfate, phosphate and hydrogen). If the kidneys are less able to excrete these substances, extracellular fluid and blood volumes increase. High buildups of wastes in the blood can make a person feel sick.

Kidney disease is the most common cause of secondary hypertension (high blood pressure). Cardiovascular disease is the major cause of death for all people with chronic kidney disease.

Even subtle disruptions in kidney function play a role in most, if not all, cases of high blood pressure and increased injury to the kidneys. If kidney disease progresses, it may lead to kidney failure, which requires dialysis or a kidney transplant to maintain life.

"There is evidence that smokers with health conditions like diabetes or high blood pressure progress to kidney disease faster than nonsmokers," Jaimes said. "It's not clear which of the many components in cigarette smoke causes this, so we decided to perform our experiments to try to clarify the role that nicotine may have."

For the first time, Jaimes and researchers at the Miami VA Medical Center identified nicotine receptors on human mesangial cells. These cells are in the kidneys' filtering units called the glomeruli.

"Often, if there is disease, the mesangial cells get activated, which produces collagen and fibronectin. This results in kidney scarring and progressive kidney disease," Jaimes said.

The researchers then examined the effect of nicotine on the mesangial cells. They added nicotine to the cells at a concentration similar to what could be expected in the blood of smokers (based on published literature).

Exposure to nicotine increased mesangial cell proliferation by 50 percent to 80 percent. Researchers measured mesangial cell proliferation by the ability to incorporate 3H-thymidine -- a radioactive marker commonly used to assess mesangial cell proliferation. Cells without nicotine incorporated 931 counts per minute (cpm) of 3H-thymidine, while cells exposed to nicotine incorporated 3H-thymidine at 1318 cpm.

Researchers also measured the level of scarring, or fibrosis, related to nicotine exposure by examining the production of fibronectin, a protein associated with scarring. They found nicotine increased the production of fibronectin by about 50 percent as measured by western blot analysis, a laboratory procedure that detects proteins in a given sample of tissue, then measures protein levels with a specialized light meter. Cells with no nicotine had 36 relative light units (RLU), while cells exposed to nicotine had 51 RLU.

When researchers exposed the cells to a compound that blocked nicotine receptors specifically, the effects of nicotine were reduced -- suggesting that the effects were mediated by nicotine. "This may be a possible mechanism for how smoking increases the risk of kidney disease," Jaimes said.

Co-authors are R. Tian, M.D.; J.Nigro, B.S.; and L. Raij, M.D.

The study was funded by a grant from the Flight Attendants Medical Research Institute, a Merit Award from the Veterans Affairs Administration and a grant from the National Institutes of Health.