Partial adherence to antihypertensive therapy fails to achieve full cardiovascular benefits in hypertensive rats

Am J Med Sci. 2008 Jun;335(6):420-5. doi: 10.1097/MAJ.0b013e31815720a9.

Abstract

Background: Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension.

Methods: Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined.

Results: Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any.

Conclusions: The results demonstrate that partial adherence to therapy reduces arterial pressure, but may not prevent target organ damage. If replicated in humans, these results may have important clinical implications in hypertensive patients.

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Biphenyl Compounds
  • Body Weight / drug effects
  • Disease Models, Animal
  • Drug Administration Schedule
  • Hemodynamics / drug effects*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Organ Size / drug effects
  • Patient Compliance*
  • Rats
  • Rats, Inbred SHR
  • Tetrazoles / administration & dosage*
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*

Substances

  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan