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July 1, 1993Journal of Hypertension

Chronic angiotensin II type 1 receptor antagonism in genetic hypertension: effects on vascular structure and reactivity

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Why the study?

Does losartan reduce cardiovascular hypertrophy and abnormal vascular amplifier properties in spontaneously hypertensive rats?

Population

14-week-old spontaneously hypertensive rats with established hypertension and age-matched Wistar-Kyoto rats

Comparison

Losartan for 6 weeks vs Untreated SHR levels and normotensive WKY rats

Design

Preclinical

Follow-up

6 weeks of treatment and 3 months post-treatment

Authors

COC.J. OddieThe Alfred HospitalRDRodney J. DilleyThe University of Western AustraliaPKPeter KanellakisBaker Heart and Diabetes Institute

Discussion

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Overview

Losartan effects on SHR hypertrophy and vascular properties wane after withdrawal; leaves open optimal regimens for durable remodeling in genetic hypertension models.

Key Points

  • To evaluate the role of angiotensin II in maintaining cardiovascular hypertrophy and abnormal vascular amplifier properties in spontaneously hypertensive rats with established hypertension.
  • Administered oral losartan for 6 weeks to 14-week-old spontaneously hypertensive rats (60 mg/kg per day) and age-matched normotensive Wistar-Kyoto controls (20 mg/kg per day).
  • Assessed systolic blood pressure, left ventricular-to-body weight ratio, medial cross-sectional areas of the abdominal aorta and mesenteric arteries, and hindquarter perfusion reactivity at the end of treatment and after a 3-month drug-free period.
  • Losartan reduced systolic blood pressure, left ventricular hypertrophy, and aortic cross-sectional area to normotensive control levels, while mesenteric artery hypertrophy decreased to a lesser extent.
  • Treatment normalized the abnormal hindquarter vascular amplifier properties in hypertensive rats, but blood pressure returned to baseline levels and cardiovascular hypertrophy partially redeveloped 3 months after stopping losartan.

Structured PICO

Does losartan reduce cardiovascular hypertrophy and abnormal vascular amplifier properties in spontaneously hypertensive rats?

P
Population
14-week-old spontaneously hypertensive rats (SHR) with established hypertension and age-matched Wistar-Kyoto (WKY) rats
I
Intervention
Losartan (60 mg/kg per day orally for SHR, 20 mg/kg per day orally for WKY) for 6 weeks
C
Comparator
Untreated SHR levels and normotensive WKY rats
O
Outcome
Systolic blood pressure, cardiac hypertrophy (ratio of left ventricular wall plus septum weight to body weight), vascular morphology (medial cross-sectional areas of abdominal aorta and mesenteric arteries), and hindquarter vascular amplifier properties at the end of 6 weeks treatment and 3 months latersurrogate

Angiotensin II type 1 receptor antagonism with losartan temporarily reverses cardiovascular hypertrophy and abnormal vascular amplifier properties in genetically hypertensive rats, but effects are not fully sustained after treatment withdrawal.

Cite This Study

Oddie et al. (1993) studied this question.

synapsesocial.com/papers/6a758c3a1cd7cac2185ffc4chttps://doi.org/10.1097/00004872-199307000-00006
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effect of AT1 Angiotensin-Receptor Blockade on Structure and Function of Small Arteries in SHR1997 · 85 citations
  2. 2Molecular Mechanism of Angiotensin II Type I and Type II Receptors in Cardiac Hypertrophy of Spontaneously Hypertensive Rats1997 · 53 citations
  3. 3Role of angiotensin II in early cardiovascular growth and vascular amplifier development in spontaneously hypertensive rats1997 · 5 citations
  4. 4Acute myocardial and vascular responses to specific angiotensin II antagonism in the spontaneously hypertensive rat1995 · 8 citations
  5. 5Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists2005 · 117 citations