Chronic Nicotine (NIC) Aggravates Sub Pressor Angiotensin II (SP‐AngII)‐Induced Renal Hemodynamics And Resistance Vessel Remodeling

Abstract

Smoking can worsen SP‐AngII induced chronic kidney disease (CKD). However, the mechanism behind this is equivocal. We hypothesized that NIC remodels the renal resistance vessels, worsening the hemodynamic parameters and hence contributes to the eventually deterioration of CKD. Male SD rats were pretreated for 12 days with NIC (12.5μg/ml) or vehicle (saccharine 2%) in water and then randomized into 4 groups: 1) Control (Cont), 2) NIC, 3) SP‐AngII (200ng/kg/min), 4) SP‐AngII + NIC. Each group received either vehicle or SP‐AngII by SQ osmotic minipumps, for an additional 22 days. Renal hemodynamics were measured in anesthetized animals, the kidneys harvested for morphometric analysis of afferent arteriole (Af‐Art) remodeling. Groups Proteinuria (mg/24 hrs) Medial Layer of Af‐Art (μm2) Lumen of Af‐Art (μm2) Media/Lumen ratio RVR (ml/min/mmHg) CRVR (TPU/mmHg) MVR (TPU/mmHg) Cont 19±1.2 124.3±12 144.5±6.3 1.13±0.1 16.2±2.5 2.6±0.2 4.5±0.2 NIC 34±4.4* 130.0±11 156.7±6 0.82±0.1 15.7±0.5 2.5±0.19 4.9±0.2 SP‐AngII 99±8.9† 253.1±11† 75.69±2.4† 3.55±0.2† 23±1.6† 3±0.17 6.6±0.2† SPAngII+NIC 150±6.5#† 321.3±10#† 31.53±2#† 11.98±1#† 32±2#† 3.6±0.2#† 9.5±0.4#† p< 0.05: * vs. Veh; # vs. SP‐AngII; † vs. NIC NIC worsened the SP‐AngII‐induced renal damage, and exacerbates the vascular resistance vessel remodeling that may contribute to the worsening hemodynamic parameters and eventually deterioration of Sp‐AngII‐ induced CKD.