Chronic Nicotine Worsens Blood Pressure and Renal Injury on Hyperandrogenemic Female Rats

Abstract

Polycystic ovary syndrome (PCOS) affects to 5?7% of reproductive-age women. It is characterized by hyperandrogenemia, insulin resistance, metabolic dysfunction, and cardiovascular and renal complications. Approximately 40% of women with PCOS have current or past smoking history (vs. healthy women 13 ? 17%), that is associated with worsening of insulin resistance and metabolic dysfunction. However, whether nicotine worsens renal injury and exacerbates the elevated blood pressure in PCOS women is unknown. We have a well-characterized model of PCOS, the hyperandrogenemic female rat (HAF rat) that mimics the cardiovascular and metabolic dysfunction present in PCOS women. In the present study, we tested the hypothesis that chronic nicotine in HAF rats worsens renal injury and hypertension. Virgin female rats were implanted with dihydrotestosterone (pellets DHT: 7.5 mg/90 d pellet, sc: HAF rats) or placebo pellets (controls: Ctr) beginning at 4?5 weeks of age. Chronic nicotine (Nic: 12.5 ug/ml) or vehicle (Veh: Sweet'n Low 2%) in drinking water was given to placebo and HAF rats (n=3/gpr) for 28 days beginning at 14 weeks of age. Mean arterial pressure (MAP, by telemetry) was measured for 7 days and at the end of this period, 24h urine and plasma samples were collected. Cotinine levels were higher in both groups treated with Nic. Nic increased proteinuria and plasma creatinine in HAF rats compared to Ctr rats (Plasma Crea: Ctr+Veh: 0.23±0.04 mg/dl vs. Ctr+Nic: 0.37±0.13 mg/dl and HAF+Veh: 0.82±0.08 mg/dl vs. HAF+Nic: 1.17±0.08 mg/dl). Also, chronic Nic exacerbated MAP only in HAF rats (Ctr+Veh: 102±1 mmHg vs. Ctr+Nic: 104±1 mmHg, p=NS; HAF+Veh: 110±1 mmHg (p<0.05 vs untreated control vs. HAF+Nic: 115±2 mmHg; p<0.05, vs HAF vehicle). These data suggest that chronic Nic may contribute to increased cardiovascular and renal disease in women with PCOS. Preclinical studies into possible mechanisms by which Nic induces its effect are needed.