cyclic-gmp and candesartan-cilexetil

To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF).. Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF.. Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP.. Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group.. These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Atrial Natriuretic Factor; Benzimidazoles; Biomarkers; Biphenyl Compounds; Cell Adhesion Molecules; Cyclic GMP; Female; Heart Failure; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Stroke Volume; Tetrazoles; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Topics: Angiotensin Receptor Antagonists; Animals; Atrial Natriuretic Factor; Benzimidazoles; Biphenyl Compounds; Cyclic GMP; Disease Models, Animal; Dogs; Endothelin Receptor Antagonists; Endothelins; Heart Failure; Polysaccharides; Receptors, Atrial Natriuretic Factor; Renin-Angiotensin System; Tetrazoles; Water-Electrolyte Balance

To evaluate the effects of endogenous angiotensin II (ANG II) on the development of congestive heart failure (CHF), we examined cardiorenal and hormonal factors after chronic administration of the ANG II type 1 receptor antagonist TCV-116 in dogs with CHF induced by rapid right ventricular pacing. After 8 days of pacing, TCV-116 administration [1 (group 1) or 3 mg.kg-1.day-1 (group 2)] was started and continued until the 22nd day. TCV-116 was found to have protected the deterioration of cardiorenal functions and the activation of neurohormonal factors. Although there was no significant difference in the pulmonary capillary wedge pressure or plasma atrial natriuretic peptide (ANP) level between the TCV-116-treated groups (354 +/- 85 and 364 +/- 29 pg/ml for groups 1 and 2, respectively) and the vehicle group (385 +/- 20 pg/ml), the plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a second messenger of ANP, were twofold higher in TCV-116-treated groups (49.4 +/- 10.2 and 50.6 +/- 7.7 pmol/ml for groups 1 and 2, respectively) than in the vehicle group (24 +/- 4.0 pmol/ml), with a high correlation between the plasma ANP and cGMP levels (r = 0.90; P < 0.05). These findings indicate that endogenous ANG II has important roles in hemodynamics and renal functions during the development of CHF, which may be due, in part, to a reduction in endogenous ANP activity, suggesting the usefulness of an ANG II-receptor antagonist against the development of CHF.

Topics: Aldosterone; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Benzimidazoles; Biphenyl Compounds; Cyclic GMP; Dogs; Female; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Kidney; Male; Norepinephrine; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Time Factors; Vascular Resistance