Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure

AIM: To investigate whether the endothelin ETA receptor blocker provides similar benefit on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure (CHF). METHODS: Male stroke-prone spontaneously hypertensive (SHR-SP) rats were subjected to permanent ligation of the left coronary artery and were treated for 6 weeks with the endothelin ETA receptor blocker LU 135252 (30 mg.kg(-1).d(-1)) starting 24 h after ligation or untreatment. Sham-operated rats served as normal controls. The mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular contractility (LV dp/dt(max)), left ventricular inner diameter (LVD) and circumference (LVC), septal thickness, left ventricular interstitial collagen content (ICC) and heart weight (HW) were measured at the end of the treatment. RESULTS: Compared with the untreated group, LU 135252 tended to increase HW (1.43 +/-0.03 vs 1.38 +/-0.04 g; P> 0.05), increased LVD (7.65+/-0.24 mm vs 6.58+/-0.14 mm; P<0.05), markedly increased LVC (30.11+/-0.83 mm vs 24.82+/-0.85 mm; P< 0.01) and reduced left ventricular ICC (3.79%+/-0.09% vs 6.71%+/-0.11%; P< 0.01), slightly lowered MAP (132+/-6 mmHg vs 142+/-4 mmHg; P>0.05), reduced LVEDP (14 4 mmHg vs 27+/-4 mmHg; P<0.05) and improved LV dp/dtmax (4230+/-450 mmHg/s vs 1950+/-400 mmHg/s; P<0.05); survival was not prolonged significantly (13% vs 11%; P=NS). CONCLUSION: In this hypertensive rat model of CHF, chronic endothelin ETA receptor blockade with LU 135252 improves cardiac hemodynamics, however, it does not affect long-term survival and worsens cardiac remodeling. Thus, endothelin ETA receptor antagonists are unlikely to have an important role in the management of patients with CHF.     

Peptiderge (NPY,NT, VIP,SP, CGRP) Innervation der funktionellen Systeme des Uterus und der Tube des Menschen

Summary With the use of immunohistochemistry NPY-IR, NT-Ir, VIP-IR, SP-IR and CGRP-IR nerve fibers were localized in the human uterus and oviduct. Each peptide showed a characteristic distribution pattern and the respective nerve fibers innervated in distinct manners the different target cell systems, i. e. surface epithelium, vasculature and smooth muscle layers. The functional implications of our results are discussed.      

Neurotensin and substance P immunoreactive nerve endings in the guinea pig carotid sinus and their ultrastructural counterparts

Summary The carotid sinus of the guinea pig was analysed immunohistochemically for the occurrence of neuropeptides. Immunoreactivity (IR) for neurotensin (NT) and substance P (SP) is distributed in two different populations of nerve endings and varicosities. NT-IR fibers penetrate deeply into the tunica media of the elastic segment of the carotid sinus and form the large, branched lanceolate nerve terminals. Electron-microscopic investigations have revealed that the NT-IR varicosities correspond to the large afferent baroreceptor endings containing abundant mitochondria. SP-IR fibers are located mainly at the mediaadventitial border. They seem to be correlated to dense-core, vesiclecontaining varicosities identified in the electron microscope. Therefore, these fibers may constitute afferent and efferent perivascular plexus regulating the vascular tone of the carotid sinus wall.This paper is dedicated to Prof. Dr. R. Ortmann on the occasion of his 70th birthday