This study investigated whether each part of the heart is evenly nnervated by the left or right vagus and observed the echanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and ±dp/dt max all ecreased one week fter left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. Western blot analyses revealed that the expression of M2 receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 μg/kg) on LVSP and ±dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M2 muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility.

The objective of this study was to clarify the relationship between angiotensin II and the pathogenesis of diabetic cardiomyopathy by observing the effects of related drugs on diabetic cardiomyopathy in rats. Captopril and Valsartan, an automatic biochemical analyzer, and radioimmunoassay technology were used to an experimental rat model of diabetic cardiomyopathy to dynamically measure the levels of creatine kinase-MB, lactate dehydrogenase-1 in the serum, and angiotensin I and II in the plasma, and to observe changes in the myocardial ultrastructure. The content of angiotensin I and II was increased and the renin–angiotensin system was in a hyperfunctional state in experimental rats with myocardial damage. Angiotensin-converting enzyme inhibitors and angiotensin II receptor 1 antagonists improved the myocardial structure and cardiac function. It is concluded that hyperfunction of the renin–angiotensin system is involved in the pathogenesis of diabetic cardiomyopathy,with an increase in angiotensin being a key factor. Preventing the increase in angiotensin II or the action of angiotensin II on its receptor can prevent the occurrence and development of diabetic cardiomyopathy.

Heart failure is correlated with attenuation of parasympathetic nervous function and enhanced sympathetic activity. Carvedilol, a thirdgenerationh-blocker, may improve the prognosis of heart failure better than selective β1-blockers. Not all of its effects, however, can be explained by direct actions on the sympathetic nervous system. This study was therefore performed to investigate the possible alterations of muscarinic cholinergic (M)2 receptors and cholinesterase-positive nerves in different regions of the adriamycin-induced failing rat heart, and the potential effects of carvedilol on these M2 receptors and cholinesterase-positive nerves. Karnovsky–Roots histochemical staining combined with point counting methods, and immunochemical streptavidin–biotin complex staining and image analysis were used to test the distribution of cholinesterase-positive nerves and the expression of M2 receptors, respectively. Our results show that the cholinesterasepositive nerve system was downregulated in the adriamycin-induced failing heart group, while the density of M2 receptors was increased in the carvedilol 3- and 10-mg/kg body weight groups, especially in the endocardial tissues of the left-ventricular free wall. It is concluded that upregulation of M2 receptors may be one of the potential mechanisms by which carvedilol exert its action on heart failure.

In this study, protective effects of adenosine and acetylcholine-induced postconditioning were investigated on the contractile function of the ischemic isolated rat ventricular myocytes. A video-based edge-detection system was used to monitor single ventricular myocytes contraction. Adenosine and acetylcholine were administrated for 6 min before ischemia as preconditioning, or 15 min after ischemia as postconditioning. Adenosine and acetylcholine receptor antagonists and mitoKATP inhibitor were used to analyze pathways underlying the effects on postconditioning. Results: (1) The peak shortening of ischemic heart cells was improved by both adenosine and acetylcholine during preconditioning (84.72±5.34% and 68.61±8.10% vs. control: 8.43±5.35% of the pre-ischemia value), as well as postconditioning (76.47±7.87% and 57.48±6.97% vs. control: 8.43±5.35% of the pre-ischemia value) and the effects of preconditioning and postconditioning were comparable. More datum in the normal text. (2) Observed effects of adenosine and acetylcholine postconditioning were missing in the presence of adenosine A1 receptor and muscarinic M2 receptor antagonists, respectively. (3)Adenosine and acetylcholine-induced postconditioning was also blocked by mitoKATP antagonist. These results suggest that both adenosine and acetylcholine protect the contractile function of ischemic heart cells to a similar extent during preconditioning and postconditioning. The postconditioning of adenosine and acetylcholine is relative to the adenosine A1 and muscarinic M2 receptors, respectively. MitoKATP is implicated in the postconditioning of both acetylcholine and adenosine.

A direct negative inotropic effect of acetylcholine on rat ventricular myocytes. Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H1393-H1400, 1993.-Acetylcholine (ACh) decreasedth e contraction of rat ventricular cells within 20s. ACh (3.1x lossM) produced a half-maximal effect and lo+ M ACh p ro d uced a maximal effect (a 23.8 t 5.4% decrease; meant SE, n=11). During a 3-min exposure to ACh, the inotropic effect faded. Parallel changes were observed in action potential duration: ACh caused an immediate shortening of the action potential, but then the effect faded with time. The changes in action potential duration were the cause of the changes in contraction, because ACh had no effect on contraction when the contractions were triggered by voltage-clamp pulses of constant duration. The changes in action potential duration were the result of the activation of a K+ current (i K ACh) by ACh. During an exposure to ACh, this current faded as a result of desensitization. iK,ACh was 6.3 times smaller in ventricular than in atria1 cells. This may explain why the negative inotropic effect of ACh on atria1 cells was greater: 1.0