Blood pressure, endothelial dysfunction and target organ injury

L. Raij, H. Hayakawa

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The architectural changes in the kidney, heart and vessels that occur in hypertension are often maladaptive and can eventually contribute to end-organ disease, such as renal failure, heart failure and coronary artery disease. The endogenous vasodilatory and antithrombotic agent nitric oxide (NO) is synthesized in the endothelium by a constitutive nitric oxide synthase (NOS). NO inhibits growth-related responses to injury in vascular cells; the effects of NO are antagonistic to those of angiotensin II. We studied the relationship between endothelial dysfunction and cardiorenal injury in hypertensive Dahl salt-sensitive (DS) rats which are a paradigm of salt-sensitive hypertension in humans. DS rats given high dietary salt (4% NaCl) developed hypertension, which was associated with impaired endothelium-dependent relaxations (EDRs) in aortic rings and mesenteric vessels. They also demonstrated left ventricular hypertrophy (LVH), glomerular injury, and increased urinary protein excretion and depressed NOS activity in the aorta. Treatment with the angiotensin-converting enzyme perindopril did not affect systolic blood pressure (SBP) but modestly improved EDR as well as proteinuria and glomerular histology. The diuretic indapamide reduced SBP and normalized EDR and LVH but did not provide complete renal protection. The fixed combination of perindopril acid indapamide normalized SBP, EDR, LVH and proteinuria and prevented glomerular injury. NOS activity in aortas was also normalized by this fixed combination. These studies suggest that the specific fixed combination of these two antihypertensive agents not only increased effectiveness in reducing blood pressure, but also maximized end-organ protection.

Original languageEnglish (US)
Pages (from-to)L44-L49
JournalEuropean Heart Journal, Supplement
Issue numberL
StatePublished - 1999
Externally publishedYes


  • Glomerular injury
  • Hypertension
  • Left ventricular hypertrophy
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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