1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank-Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with alpha(1A)-adrenoceptors identified as a major component of SNS and AT(1) receptors of RAS to induce vasopressor effects.
Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.