Effect of nicotine on the renal microcirculation in anesthetized rats: a potential for medullary hypoxic injury?
BACKGROUND
Cigarette smoking has been associated with accelerated renal dysfunction among patients with chronic renal disease. Conceivably, repeated parenchymal hypoxic injury, induced by nicotine-related vasomotor changes, might contribute to the progression of renal failure in smokers.


METHODS
Renal blood flow and selective cortical and outer medullary blood flows were determined in anesthetized rats. Changes in total renal, cortical and medullary vascular resistance were calculated. Nicotine was repeatedly infused at rising doses (50-200 microg/kg) to intact (CTR) animals and to rats chronically administered with nicotine in their drinking water (NIC). In a complementary study, nicotine-treated and control rats were subjected to medullary hypoxic stress, induced by radiocontrast and indomethacin.


RESULTS
Chronic nicotine exposure led to lower baseline renal blood flow and creatinine clearance. Nicotine infusion induced a transient dose-dependent rise in blood pressure, renal blood flow and cortical flow, with a corresponding decline in renal vascular resistance and cortical resistance in both experimental groups. However, while medullary flow increased in CTR by up to 16 +/- 6%, it remained unchanged or even somewhat declined in the NIC group. Calculated medullary resistance reciprocally declined in CTR while it rose in the NIC group (p < 0.001). In animals subjected to radiocontrast and indomethacin, nicotine intensified renal dysfunction, associated with focal medullary hypoxic damage.


CONCLUSIONS
Chronic exposure to nicotine selectively compromises the outer medullary microcirculation, blunting a local vasodilatory response to acute nicotine administration. Repeated acute-on-chronic exposure to nicotine may predispose to hypoxic medullary injury.
Heyman
Samuel N
SN
Department of Medicine, Hadassah-Hebrew University Medical Center, Mt. Scopus, Jerusalem, Israel. Heyman@cc.huji.ac.il
Goldfarb
Marina
M
Rosenberger
Christian
C
Shina
Ahuva
A
Rosen
Seymour
S
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000652:urine; D000818:Animals; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced*; D007674:Kidney Diseases / Q000139:chemically induced*; D007679:Kidney Medulla / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D018722:Nicotinic Agonists; D009538:Nicotine; D003404:Creatinine