title: Low-dose lithium combined with captopril prevents stroke and improves survival in salt-loaded, stroke-prone spontaneously hypertensive rats.
abstract: OBJECTIVE
  A number of potential interactions between angiotensin-converting enzyme inhibitors and lithium have been described in the literature. In the present study, we investigated the effects of a low-dose combination treatment with lithium and captopril on survival and stroke prevention in salt-loaded, stroke-prone spontaneously hypertensive rats (SHRSP).
  
  
  METHODS
  Eight-week-old saline-drinking SHRSP (n = 21 per group) were treated with vehicle, LiCl (1 mmol/kg per day), captopril (25 mg/kg per day) and captopril plus LiCl for up to 37 weeks. Body weight, salt water intake blood pressure and mortality were recorded throughout the experimental period. Plasma renin activity, plasma lithium concentration and urinary excretion of albumin, sodium and potassium were measured at different time points.
  
  
  RESULTS
  Captopril treatment doubled the life expectancy when compared with vehicle-treated rats. Lithium alone had minor effects on survival but led to a dramatic increase in survival when added to captopril (mean survival time > 237 versus 147 days, P < 0.001). Systolic blood pressure increased with age in all treatment groups but was comparable in the captopril-treated and the captopril-plus-lithium-treated groups. Plasma renin activity as well as urinary sodium and potassium excretion did not differ between both groups. In the captopril group a striking fivefold increase of albuminuria occurred between 14 and 26 weeks of age, while this progression was completely abolished by the addition of lithium.
  
  
  CONCLUSIONS
  Our results demonstrate that the addition of lithium to captopril dramatically prolong the effects of the angiotensin-converting enzyme inhibitor on survival in salt-loaded SHRSP. This effect was independent of a reduction in blood pressure.
authors.affiliation: Institute of Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Jihong
authors.initials: J
authors.lastname: Xu
authors.forename: Annedore
authors.initials: A
authors.lastname: Scholz
authors.forename: Nicole
authors.initials: N
authors.lastname: Rösch
authors.forename: Annegret
authors.initials: A
authors.lastname: Blume
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Juraj
authors.initials: J
authors.lastname: Culman
authors.forename: Peter
authors.initials: P
authors.lastname: Gohlke
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008094:Lithium / Q000097:blood; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D012982:Sodium, Dietary; D008094:Lithium; D002216:Captopril; D012964:Sodium; D012083:Renin; D018021:Lithium Chloride; D011188:Potassium