Changes in peptidergic nerves in the atrioventricular valves of streptozotocin-induced diabetic rats: A confocal microscopy study

Abstract

Several previous studies have described the distribution of neuropeptide Y (NPY)-like and calcitonin gene related peptide (CGRP)-like immunoreactive nerve fibres in the atrioventricular valves of humans and various animals. It has been suggested that peptide-containing nerve fibres might have motor or sensory roles in valvular function. Although there is evidence that diabetic changes occur in the sympathetic (preganglionic and postganglionic), parasympathetic (vagal) and peptidergic nerves of rats, the changes of peptide-containing nerve fibres in the atrioventricular valves of the diabetic rat have not been studied. The distribution, relative density and staining intensity of NPY-like and CGRP-like immunoreactive nerve fibres in the mitral and tricuspid valves were studied in whole mount preparations using confocal microscopy with a computer-assisted image analysis system. Streptozotocin-induced diabetic and control rats were sacrificed at 12 and 24 months. The nerve staining intensity within the tricuspid valve was greater than the mitral valve in both control (P < 0.01) and diabetic (P < 0.001) rats. Nerve density in the anterior leaflet was greater than the posterior leaflet of the mitral valve. However, the anterior leaflet of the mitral and tricuspid valves showed a decreased number of nerve fibres, followed by drastic reduction in the staining intensities for both the peptides studied (P < 0.001) in the long-term diabetic rat. The decrease in the number of nerve fibres that follow the mechanical interruption of nerves raises the possibility that cycles of degeneration may occur. It is suggested that these peptide-containing nerve fibres in the atrioventricular valves may be involved in valvular dysfunction in the diabetic state.

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

“…28–30 The occurrence and distribution of different neurotransmitters and neuromediators were investigated in the heart in different species of animals by investigating the presence of acetylcholine, 23,31 nitric oxide, neuropeptide Y, tyrosine hydroxylase and calcitonin gene related peptide. 1,31–34 …”

“…The anterior leaflet of mitral valve, as a neurally-controlled tissue, provides thus a clinically relevant model for the investigation of functional role of nervous system in normal and abnormal heart valve action. 1,5,30 …”