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Prevention and regression of hypertension: role of renal microvascular protection

Hiroyuki Sasamura1, Kaori Hayashi, Kimiko Ishiguro

  • 1Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan. sasamura@sc.itc.keio.ac.jp

Hypertension Research : Official Journal of the Japanese Society of Hypertension
|June 13, 2009
PubMed

Insights

High-dose angiotensin receptor blockers (ARBs) can reverse established hypertension in animal models, suggesting potential for regression of high blood pressure even after the critical developmental period.

Area of Science:

  • Cardiovascular Research
  • Nephrology
  • Pharmacology

Background:

  • Hypertension affects over 26.4% of the global adult population, necessitating innovative prevention and treatment strategies.
  • Previous research indicates renin-angiotensin system (RAS) inhibitors can prevent hypertension development during critical periods in animal models and humans.
  • Recent findings suggest 'pulse' treatment with high-dose angiotensin receptor blockers (ARBs) may reduce established hypertension in spontaneously hypertensive rats (SHR).

Purpose of the Study:

  • To investigate the potential for regression of established hypertension using high-dose ARBs.
  • To examine the effects of ARBs on renal arteriolar hypertrophy in animal models.
  • To initiate a prospective, multicenter clinical study (STAR CAST) to evaluate hypertension regression in humans.

Main Methods:

  • Treatment of spontaneously hypertensive rats (SHR) with ARBs during and after the critical period of hypertension development.
  • Assessment of established hypertension reduction and renal arteriolar hypertrophy.
  • Analysis of microvascular matrix metalloproteinase (MMP) expression in response to ARB treatment.

Main Results:

  • High-dose ARB 'pulse' treatment effectively reduced established hypertension in SHR, even when initiated after the critical period.
  • ARB treatment during the critical period inhibited renal arteriolar hypertrophy development.
  • High-dose ARB administration led to significant reversal of renal arteriolar hypertrophy in SHR, linked to altered microvascular MMP expression.

Conclusions:

  • Established hypertension may be reversible with high-dose ARB therapy.
  • Renal microvascular changes, including hypertrophy and MMP expression, play a crucial role in hypertension prevention and regression mediated by ARBs.

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