The central vasopressinergic system in experimental left ventricular hypertrophy and dysfunction.
In the course of cardiac diseases, various neuruhomonal systems in the plasma are activated. So far there have been only isolated results of investigations about the functional state of central neuropeptide systems in cardiac diseases and, in particular, in heart failure. We investigated, therefore, the central vasopressinergic system, an important neuropeptide system in cardiocirculatory regulation in a model of myocardial hypertrophy and left ventricular dysfunction, a model of supravalvular aortic stenosis. In addition to increased vasopressin concentrations in plasma, central vasopressin is also altered in this model. A differential stimulation of vasopressin in the hypothalamic areas and in the areas of the brain stem that are involved in central cardiocirculatory regulation was detected. Reduced vasopressin concentrations in the locus coeruleus, an important regulatory area of sympathetic nervous activity, suggest a central regulatory mechanism through which stimulation of the sympathetic nervous activity can be prevented. Our investigations showed that non-osmotic factors like the baroreceptor reflex and angiotensin II, are important stimuli of the vasopressinergic system. We were also able to show that the central vasopressinergic system in rats with experimental heart failure and myocardial hypertrophy is inhibited by treatment with an ACE inhibitor and AT1 receptor antagonist. As seen with autoradiography, this effect is mediated by a central effect of the drugs. Research into central regulatory mechanisms in cardiovascular diseases is, on the one hand, of crucial importance to our understanding of complex pathophysiological processes, and on the other hand, it serves the development of new therapeutic approaches with the goal of influencing these mechanisms directly pharmacologically and for the elucidation of central, currently unknown effects of cardiovascular drugs.
Muders
Frank
F
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany. frank.muders@klinik.uni-regensburg.de
Riegger
Günter A J
GA
Bahner
Udo
U
Palkovits
Miklos
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D004195:Disease Models, Animal; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology*; D014667:Vasopressins / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065092:Antidiuretic Hormone Receptor Antagonists; D014667:Vasopressins