Antihypertensive action of indapamide. Comparative studies in several experimental models.
1-(4-Chloro-3-sulfamylbenzamido)-2-methyl-indoline (indapamide), after single oral dose administration, showed antihypertensive activity in genetically hypertensive rats, DOCA/saline hypertensive rats, unilaterally-nephrectomised DOCA/saline hypertensive rats and dogs made hypertensive by renal encapsulation. The activity was observed at doses as low as 1-3 mg/kg and lasted at least 48 h. Increasing the dose level considerably prolonged the duration of action but did not substantially enhance the maximum antihypertensive effect. In genetically hypertensive rats indapamide was 30-300 times more potent than furosemide, spironolactone and chlorthalidone. Indapamide had no effect on blood pressure in normotensive rats. In concentrations of 1 X 10(-5) to 1 X 10(-3) g/ml, indapamide antagonised contractions of arterial and venous strips to angiotensin, epinephrine and norepinephrine revealing a direct vascular action. Indapamide has a prolonged saluretic action which in combination with the direct vascular effects may well account for its antihypertensive activity.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D006973:Hypertension / Q000188:drug therapy; D006977:Hypertension, Renal / Q000188:drug therapy; D007190:Indapamide / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009392:Nephrectomy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000187:drug effects
D000959:Antihypertensive Agents; D004232:Diuretics; D013148:Spironolactone; D005665:Furosemide; D007190:Indapamide; D002752:Chlorthalidone