J.‐B. Osnes

ROLE OF CYCLIC ADENOSINE 3‘,5’‐MONOPHOSPHATE IN THE ISOPRENALINE‐INDUCED RELAXATION OF THE OESTROGEN DOMINATED RABBIT UTERUS

1 The role of cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated. 2 Isoprenaline 2 × 10−8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 × 10−6 M produced both inhibition of mechanical activity and increase in cyclic AMP. 3 The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 × 10−6 M. 4 Dibutyryl‐cyclic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones. 5 It is concluded that cyclic AMP may be a mediator of the β‐adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of β‐adrenoceptors and relaxation. Other mechanisms may also exist.

SERCA2 activity is involved in the CNP-mediated functional responses in failing rat myocardium

Myocardial C‐type natriuretic peptide (CNP) levels are increased in heart failure. CNP can induce negative inotropic (NIR) and positive lusitropic responses (LR) in normal hearts, but its effects in failing hearts are not known. We studied the mechanism of CNP‐induced NIR and LR in failing hearts and determined whether sarcoplasmatic reticulum Ca2+ ATPase2 (SERCA2) activity is essential for these responses.

Cyclic AMP‐dependent inotropic effects are differentially regulated by muscarinic Gi‐dependent constitutive inhibition of adenylyl cyclase in failing rat ventricle

BACKGROUND AND PURPOSE β‐Adrenoceptor (β‐AR)‐mediated inotropic effects are attenuated and Gi proteins are up‐regulated in heart failure (HF). Muscarinic receptors constitutively inhibit cAMP formation in normal rat cardiomyocytes. We determined whether constitutive activity of muscarinic receptors to inhibit adenylyl cyclase (AC) increases in HF and if so, whether it modifies the reduced β‐AR‐ or emergent 5‐HT4‐mediated cAMP‐dependent inotropic effects.

730 The effect of Piboserod a 5‐HT4‐receptor antagonist on left ventricular function in patients with symptomatic heart failure

Standard therapy: ACEI, diuretics, cardiac glycosides, β-blockers. All patients underwent a 6-min test; evaluation of EF (echoCG); measurement of CRP in blood (EIA method); endotoxin (LAL); faeces plating on growth media; colonoscopy with fecal biopsy with subsequent histological and histochemical (OLA, Muc5, staining for CD8+ cells; Ki67) evaluation of tissue samples at 1 and 14 day of treatment. Results: At first day patients of both groups had plethoric blood vessels in the mucosal proper lamina and focal, dense lymphoid cellular infiltration corresponding to the picture of pronounced chronic inflammation. Lymphocytes were represented primarily by CD8+ cells. Also the number of mucin 5-producing glandular cells was increased. In addition, histological examination revealed abundant siderophages indicating a chronic congestive process in large intestinal blood vessels. At 1 group on 14 day – we found decreasing of chronic inflammation and edema of mucosal proper lamina. In group 2 decreasing of edema was significantly less and increasing of chronic inflammation was finding. Analyses of blood revealed significant (p<0.05) differences between two groups at 14 day: CRP 1.89±0.03 U/l and endotoxin 0.39±0.01 EU/ml in group 1 and CRP 4.6±0.07 U/l and endotoxin 1.3±0.08 EU/ml in group 2. No significant changes in faecal level of enterobacteria were finding. Conclusions: Patients with high FC CHF have chronic inflammation of large intestine, which is probably one of causes for the increased blood endotoxin and development of systemic inflammation. Additional prescription of diuretics, especially diacarb may be helpful in treatment of systemic inflammation in patients with high FC CHF.