Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.

Abstract

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

• Authors: S Gasic, O F Wagner, P Fasching, C Ludwig, M Veitl, S Kapiotis, B Jilma
• Journal: American journal of hypertension (Am J Hypertens) Vol. 12 Issue 2 Pt 1 Pg. 217-22 (Feb 1999) ISSN: 0895-7061 [Print] United States
• PMID: 10090351 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Biomarkers
• Blood Glucose
• E-Selectin
• Glycated Hemoglobin A
• Plasminogen Activator Inhibitor 1
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Peptidyl-Dipeptidase A
• Tissue Plasminogen Activator
• Fosinopril

Topics

• Adult
• Aged
• Albuminuria (blood, drug therapy, etiology)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Biomarkers (blood)
• Blood Glucose (metabolism)
• Blood Pressure (drug effects)
• Diabetes Mellitus, Type 2 (blood, complications)
• E-Selectin (blood)
• Female
• Follow-Up Studies
• Fosinopril (therapeutic use)
• Glycated Hemoglobin (metabolism)
• Humans
• Hypertension (blood, complications, drug therapy)
• Intercellular Adhesion Molecule-1 (blood)
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (blood, drug effects)
• Plasminogen Activator Inhibitor 1 (blood)
• Prospective Studies
• Tissue Plasminogen Activator (blood)
• Treatment Outcome
• Vascular Cell Adhesion Molecule-1 (blood, drug effects)