title: Inhibitory effects of sertraline in rat isolated perfused kidneys and in isolated ring preparations of rat arteries.
abstract: OBJECTIVE
  Sertraline is often prescribed to patients suffering with end stage renal disease, but its action on kidney has not been investigated. We aimed to investigate the pharmacological action of sertraline on rat kidney with emphasis on the underlying mechanisms involved in the vascular actions of the drug.
  
  
  METHODS
  The effects of sertraline were evaluated in rat isolated perfused kidneys and on ring preparations of mesenteric or segmental rat renal artery.
  
  
  RESULTS
  In kidneys, sertraline prevented the effects of phenylephrine on perfusion pressure, glomerular filtration rate, urinary flow and renal vascular resistance. In mesenteric rings sertraline inhibited phenylephrine-induced contractions with potency 30-times lower than verapamil. Sertraline reversed sustained contractions induced by phenylephrine or 60mm K(+) within a similar concentration range. In segmental isolated rings, sertraline also reversed contractions induced by phenylephrine or 60mm K(+) with the same concentration range, but with higher potency compared with mesenteric preparations. Under Ca(2+) -free conditions, sertraline did not change the intracellularly-mediated phasic contractions induced by phenylephrine or caffeine. Sertraline was ineffective against contractions induced by extracellular Ca(2+) restoration after thapsigargin treatment and Ca(2+) store depletion with phenylephrine. Conversely, sertraline decreased the contractions induced by Ca(2+) addition in tissues under high K(+) solution or phenylephrine plus verapamil.
  
  
  CONCLUSIONS
  In rat isolated kidneys and in rat ring preparations of mesenteric or renal vessels, sertraline had antispasmodic effects that appeared to be caused by a direct action on vascular smooth muscle cells. Its actions were ineffective against Ca(2+) -releasing intracellular pathways, but appeared to interfere with sarcolemmal Ca(2+) influx with reduced permeability of both receptor- and voltage-gated Ca(2+) channels.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Ceará, Brasil.
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Fonseca-Magalhães
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sousa
authors.forename: Rodrigo J B
authors.initials: RJ
authors.lastname: de Siqueira
authors.forename: Roberta J B
authors.initials: RJ
authors.lastname: Jorge
authors.forename: Gdayllon C
authors.initials: GC
authors.lastname: Meneses
authors.forename: Renata S
authors.initials: RS
authors.lastname: Alves
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
authors.forename: Pedro J C
authors.initials: PJ
authors.lastname: Magalhães
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Martins
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012508:Sarcolemma / Q000378:metabolism; D020280:Sertraline / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014554:Urination / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D014665:Vasodilator Agents; D010656:Phenylephrine; D002110:Caffeine; D019284:Thapsigargin; D014700:Verapamil; D020280:Sertraline; D002118:Calcium