Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

The pressor effect of angiotensin-(1-7) in the rat rostral ventrolateral medulla involves multiple peripheral mechanisms

OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7) in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7) (25 pmol) was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously) with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium) or a vasopressin V1 receptor antagonist [d(CH2)5 -Tyr(Me)-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7) (16 ± 2 mmHg, n = 12), which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7) at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7) at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7) triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism.

Hemodynamic Responses to Different Ventricular Pacing Sites and Pacing Rates in Dog

BACKGROUND: The hemodynamic effects of an episode of ventricular tachycardia (VT) may vary from mild decrease in blood pressure to sustained hypotension, collapse, and death. Little is known about the factors responsible for these diverse effects. Ventricular function, vasomotor tone, and tachycardia cycle length could be major determinants of variable hemodynamic responses to VT. The site of origin was found to be a factor affecting pulse pressure even in an isolated ventricular premature contraction. However, the role of origin site in hemodynamics of VT is not yet elucidated. The purposes of this study were to evaluate the effects of VT origin site and VT cycle length to their hemodynamic changes. And we also have assessed the role of cardiac autonomic receptor activation in hemodynamic recovery during and immediate after VT. METHODS: In 18 open chest dogs anesthetized with chloralose, bipolar ventricular pacing (VP) was performed using sutured epicardial electrodes at 3 different sites ; left ventricular apex (LVA), right ventricular outflow tract (RVOT), and right ventricular apex (RVA). At each site, VP was repeated for 60 seconds at 3 different rates; 1.75X, 2X, and 2.25X of baseline heart rate (BHR). Mean arterial pressure (MAP), mean left atrial pressure (MLAP) and mean pulmonary artery pressure (MPAP) were monitored during VP. deltaMAP was defined as the difference between the baseline MAP and lowest MAP during VP. deltaMLAP was defined as the difference between highest MLAP during VP and baseline MLAP. Cardiac vagal and beta-adrenoreceptor blockades were achieved by intravenous bolus administration of propranolol (1 mg/kg and then 1 mg/kg/hr) and atropine (0.5 mg/kg and then 0.5 mg/kg/hr). After cardiac autonomic blockade, VP was repeated at 2X of baseline heart rate for 60 seconds at each site. RESULTS: Baseline MAP, MLAP, and MPAP were 101+/-8.1 mmHg, 0.3+/-0.41 mmHg, and 10+/-2.4 mmHg, respectively. At the same pacing site of VP, MAP was decreased significantly with VP and deltaMAP was increased significantly as VP cycle length shortened (all P<0.001). At the same pacing cycle length of VP, deltaMAP was significantly greater at RVA or RVOT than LVA: LVA vs RVOT ; all P<0.001 at 3 different rates, LVA vs RVA ; P<0.05 (1.75X & 2X of BHR), P<0.001 (2.25X of BHR). But there was no significant difference in deltaMAP between RVA and RVOT. At the same pacing site of VP, MLAP and deltaMLAP were increased significantly as VP cycle length shortened (all P<0.01), but at the same cycle length of VP, there was no significant differences in deltaMLAP at 3 different VP sites. Ventricular pacing after autonomic blockade induced a greater increase in deltaMAP and deltaMLAP compared to controls (all P<0.01 at 3 pacing sites). And cardiac autonomic blockade also resulted in significant blunting of recovery of MAP during VP compared to controls. CONCLUSION: Above results showed that pacing cycle length plays a major role in determining the hemodynamic outcomes during ventricular pacing, and that the site of origin could be an independent factor of ventricular tachycardia hemodynamics. And also modulation of tone of the adrenergic nervous system is essentially required for the hemodynamic recovery during ventricular tachycardia.