Increased renovascular response to angiotensin II in persons genetically predisposed to arterial hypertension disappears after chronic angiotensin-converting enzyme inhibition

J Hypertens. 2004 Jan;22(1):175-80. doi: 10.1097/00004872-200401000-00027.

Abstract

Objective and methods: Functional changes in the kidneys of healthy men with (FH+) (n = 15) and without (FH-) (n = 15) family history of primary arterial hypertension were examined during administration of low-dose exogenous angiotensin II (A2) (1 ng/kg per min) before and after acute (1 mg intravenous enalaprilat) and chronic (7 days oral enalapril, 30 mg/day) angiotensin-converting enzyme (ACE) inhibition.

Results: Before chronic ACE inhibition, A2 increased mean arterial blood pressure (FH+, 8.7 +/- 0.8 mmHg; FH-, 8.9 +/- 0.9 mmHg), plasma immunoreactive A2 (FH+, 21 +/- 2 pg/ml; FH-, 18 +/- 3 pg/ml) and plasma aldosterone (FH+, 64 +/- 7 pg/ml; FH-, 56 +/- 6 pg/ml) to a similar degree in both groups. Chronic ACE inhibition had no impact on A2 blood pressure, plasma A2, or plasma aldosterone effects. A2 significantly increased renal vascular resistance in both groups (FH+, 3956 +/- 462 dyne s cm(-5); FH-, 2219 +/- 550 dyne s cm(-5)), but the effect was more pronounced in FH+ (P = 0.02). Glomerular hemodynamics, estimated by a modified Gomez model, revealed increased afferent and efferent responsiveness to A2 in FH+ subjects. These differences disappeared after chronic ACE inhibition when total, afferent and efferent sensitivities to A2 were similar in both groups.

Conclusions: Systemic blood pressure and plasma aldosterone responses to A2 were similar in men with or without a genetic disposition to primary arterial hypertension. However, our data demonstrate that men with a family history of hypertension have increased renovascular sensitivity to A2, and that chronic ACE inhibition normalizes their sensitivity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aldosterone / blood
  • Angiotensin II / administration & dosage*
  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Diastole / drug effects
  • Dose-Response Relationship, Drug
  • Genetic Predisposition to Disease / genetics*
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics*
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / metabolism
  • Male
  • Reference Values
  • Regional Blood Flow / drug effects
  • Renin / drug effects
  • Renin / metabolism
  • Systole / drug effects
  • Time Factors
  • Treatment Outcome
  • Vascular Resistance / drug effects
  • Vasoconstrictor Agents / administration & dosage*
  • Vasoconstrictor Agents / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Vasoconstrictor Agents
  • Angiotensin II
  • Aldosterone
  • Renin