Premium
EXACERBATION BY NICOTINE OF THE CYCLOSPORINE A‐INDUCED IMPAIRMENT OF β‐ADRENOCEPTOR‐MEDIATED RENAL VASODILATION IN RATS
Author(s) -
ElGowilly Sahar M,
Ghazal AbdelRheem M,
Gohar Eman Y,
ElMas Mahmoud M
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.04983.x
Subject(s) - isoprenaline , endocrinology , nicotine , medicine , chemistry , vasodilation , hexamethonium , phenylephrine , propranolol , pharmacology , atropine , blood pressure , stimulation
SUMMARY1 Nicotine is implicated in smoking‐related renovascular impairment and worsening of existing nephropathies. In the present study, we investigated whether nicotine aggravates the deleterious effect of the immunosuppressant drug cyclosporine A (CsA) on renal vasodilation induced by the β‐adrenoceptor agonist isoprenaline. 2 Bolus isoprenaline (0.03–8.0 µmol) elicited dose‐dependent vasodilation of phenylephrine‐preconstricted perfused kidneys that was attenuated by infusion at 5 mL/min of nicotine (5 × 10 −4 mol/L) or CsA (2 µmol/L). Further, chronic administration of nicotine (0.4 mg/kg per day) or CsA (20 mg/kg per day) for 3 weeks reduced isoprenaline‐induced vasodilation and elevated plasma urea and creatinine concentrations, effects that were magnified when both nicotine and CsA were administered concurrently. 3 The role of endothelial and smooth muscle signalling in the acute nicotine/CsA renovascular interaction was investigated. Vasodilation caused by 0.25 µmol isoprenaline was attenuated by 6 µmol/L propranolol and 10 mmol/L tetraethylammonium (TEA), potentiated by 100 µmol/L hexamethonium and 7 µmol/L diclophenac, and virtually abolished in 80 mmol/L KCl‐preconstricted tissues. N G ‐Nitro‐ l ‐arginine ( l ‐NNA; 200 µmol/L), methylene blue (10 µmol/L), 3‐[(3‐cholamidopropyl)‐dimethyl‐ammonio]‐1‐propane‐sulphonate (CHAPS; 0.2% for 30 s), nifedipine (750 nmol/L), atropine (1 µmol/L) and SQ22536 (an adenylyl cyclase inhibitor; 3 × 10 −5 mol/L) had no effect on isoprenaline responses. 4 Nicotine (5 × 10 −4 mol/L) reduced isoprenaline‐induced vasodilation and this effect was potentiated by concurrent CsA (2 µmol/L) infusion. Nicotine‐induced impairment of the vasodilator response to isoprenaline was reduced by hexamethonium and potentiated by l ‐NNA, methylene blue, CHAPS and nifedipine. Alternatively, CsA exacerbation of the nicotine–isoprenaline interaction was abolished by propranolol, l ‐NNA, methylene blue, CHAPS, l ‐arginine, TEA and nifedipine. 5 In summary, nicotine and CsA produce additive impairment of kidney function and β‐adrenoceptor‐mediated renovascular control, nitric oxide (NO)–cGMP signalling tonically restrains nicotine‐induced impairment of isoprenaline vasodilation and the endothelial NO–K + pathway modulates the aggravating effect of CsA on nicotine–isoprenaline interactions.