Central nervous effects of CRF and angiotensin II on cardiac output in conscious rats

Studies were performed to determine whether the central nervous system actions of corticotropin-releasing factor (CRF) and angiotensin II (ANG II) on systemic arterial pressure are mediated, in part, through changes in cardiac output (CO). Changes in CO after intracerebroventricular administration of ANG II and CRF were assessed in conscious unrestrained rats bearing pulsed Doppler flow probes on the ascending aorta. Intracerebroventricular injection of CRF (0.15 nmol) increased arterial pressure (15-20 mmHg), heart rate (70-100 beats/min), and CO (25-35%) without significantly affecting total peripheral resistance. Intracerebroventricular injection of ANG II (0.1 nmol) produced similar elevations of arterial pressure (15-20 mmHg). However, the ANG II-induced pressor response was attended by significant decreases in heart rate (20 beats/min) and CO (10-15%) and significant increases in total peripheral resistance (30-40%). The results of these studies demonstrate that CO, as assessed by pulsed Doppler flow probe methodology, may be influenced significantly and differentially by central nervous system administration of CRF and ANG II.     

Influence of sarmesin on the cardiac and vascular actions of angiotensin II

Summary The angiotensin II (ANG II) receptor blocker properties of sarmesin and its influence on the homotropic cooperativity of ANG II receptors were studied in two experimental models: isolated rabbit aorta and isolated rabbit atria. The results show that: (i) sarmesin is a specific competitive antagonist of ANG II receptors, with high affinity (pA₂=8.93 in the isolated aorta and 8.66 in the isolated atria); and (ii) the slope of the concentration-response curves to ANG II and the Hill coefficient increased in the presence of sarmesin, the latter suggesting an enhancement of the positive homotropic cooperativity of ANG II receptors. These results may be explained overall by the reciprocal negative modulation of receptor affinity between sarmesin and ANG II, due, possibly, to opposite effects on the binding of G-proteins to ANG II receptors.     

Influence of vagal cooling on cardiac output in normal and beta-blocked exercising dogs

To study the relative influence of parasympathetic and sympathetic innervation on the early adaptation of cardiac output (CO) to exercise, we determined the time constant and amplitude of the CO change in dogs following a stepwise increase in treadmill velocity. The animals were studied during control conditions, beta-blockade, vagal blockade and combined beta-blockade and vagal blockade. To measure CO, an electromagnetic flow probe was implanted around the ascending aorta. Vagal activity was blocked with coolers, implanted around the cervical vagosympathetic trunks. The time constant during beta-blockade (12.1 s) was not different from the control situation (11.4 s), but during vagal cooling it increased significantly (16.2 s), and with combined vagal cooling and beta-blockade it rose to 20.7 s. Thus the increase in cardiac output with exercise is accelerated most by the loss of vagal tone and to a lesser degree by sympathetic activation. The amplitude of the change in CO during control was 112%. Heart rate (HR) rose by 74% and stroke volume (SV) by 22%. Beta-blockade lowered the initial CO but did not alter the percentage increase. Vagal cooling, with or without beta-blockade, caused an increased initial HR but did not influence basal CO because of a concomitant reduction in SV. Exercise now increased HR less (21% and 30%, respectively) and SV more (52% and 52%) but the increase in CO did not change significantly (87% and 97%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of expiratory loading and hyperinflation on cardiac output during exercise.

Patients with obstructive lung disease are exposed to expiratory loads (ELs) and dynamic hyperinflation as a consequence of expiratory flow limitation. To understand how these alterations in lung mechanics might affect cardiac function, we examined the influence of a 10-cm H2O EL, alone and in combination with voluntary hyperinflation (ELH), on pulmonary pressures [esophageal (Pes) and gastric (Pg)] and cardiac output (CO) in seven healthy subjects. CO was determined by using an acetylene method at rest and at 40 and 70% of peak work. At rest and during exercise, EL resulted in an increase in Pes and Pg (7-18 cm H2O; P < 0.05) and a decrease in CO (from 5.3 +/- 1.8 to 4.5 +/- 1.4, 12.2 +/- 2.2 to 11.2 +/- 2.2, and 16.3 +/- 3.3 to 15.2 +/- 3.2 l/min for rest, 40% peak work, and 70% peak work, respectively; P < 0.05), which remained depressed after an additional 2 min of EL. With ELH, CO increased at rest and both exercise loads (relative to EL only) but remained below control values. The changes in CO were due to a reduction in stroke volume with a tendency for stroke volume to fall further with prolonged EL. There was a negative correlation between CO and the increase in expiratory Pes and Pg with EL (R = -0.58 and -0.60; P < 0.01), whereas the rise in CO with subsequent hyperinflation was related to a more negative Pes (R = 0.72; P < 0.01). In conclusion, EL leads to a reduction in CO, which appears to be primarily related to increases in expiratory abdominal and intrathoracic pressure, whereas ELH resulted in an improved CO, suggesting that lung inflation has little impact on cardiac function.