Activation of bradykinin-sensitive pericardial afferents increases systemic venous tone in conscious rats

Abstract

The venous system plays a critical role in blood pressure regulation by controlling venous return, cardiac filling, and cardiac output. Sympathetic drive is a major controller of venous function. However, outside of the arterial baroreflex, the mechanisms that regulate sympathetic drive to veins remain poorly defined in both physiological and disease conditions. The heart itself has an important sensory function via a variety of cardiac receptors that modulate cardiovascular function by neural and humoral reflexes. Bradykinin‐sensitive sympathetic afferent nerves from the heart can trigger marked increases in efferent sympathetic nerve activity to some cardiovascular target organs such as the kidney. This work tested the hypothesis that the activation of bradykinin‐sensitive cardiac afferents increases venous tone and cardiac output. Sprague Dawley rats were anesthetized with a cocktail of alpha chloralose (80 mg/kg) and urethane (800 mg/kg). Catheters were placed in the femoral artery and vein to record arterial and venous blood pressures. A PE 10 catheter was placed in the pericardial space for the injection of bradykinin (BK), an agent known to stimulate cardiac sympathetic afferents. In some rats, a balloon tipped catheter was placed in the right atrium to allow transient arrest of cardiac pumping for the estimation of mean circulatory filling pressure (MCFP), an estimate of systemic venous tone. In other rats, an electromagnetic flow probe was placed on the aortic arch for the direct measurement of cardiac output. In rats instrumented for the measurement of venous tone, pericardial injections of BK (0.4–20 μg/kg) were associated with dose‐related increases in mean arterial pressure (9±6 to 27±6 mm Hg) and MCFP (0.6±0.2 to 1.6±0.4 mm Hg). These responses were largely attenuated after ganglionic blockade. In rats instrumented for the measurement of cardiac output, pericardial injection of BK (10 μg/kg) increased mean arterial pressure (23±3 mm Hg) and cardiac output (16±2 ml/min). We interpret these data to indicate that activation of bradykinin‐sensitive pericardial afferents increases venous tone sufficiently to increase cardiac filling and cardiac output. Support or Funding Information Supported by NIH R01 HL136741‐01 and the Basic Biomedical Sciences program of the Sanford School of Medicine, University of South Dakota. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hemodynamic patterns associated with activation of bradykinin-sensitive pericardial afferents

“…One possibility is that the dichotomous hemodynamic responses were dependent on the balance of afferent activation produced by pericardial BK injection. It is noteworthy that our approach, which mirrored that of McDermott ( McDermott et al, 1995 ) and our previous study ( Martin et al, 2020 ), used a pericardial catheter fixed in place along the lateral left ventricle to inject into the pericardial sac. Thus, the injectate was able to circulate within the pericardial sac and likely activated different types of cardiac afferents leading to overall activation of bradykinin-sensitive pericardial afferents.…”

“…This work in male rats using pressure-volume loop analysis indicated that localized epicardial BK application increased overall systemic flow, CO, by approximately 14% ( Wang et al, 2017 ). Since we reported previously that pericardial bradykinin injection increased venous tone ( Martin et al, 2020 ), we expected increased CO in response to pericardial bradykinin injection. In fact, we observed two distinct patterns of pericardial BK-induced hemodynamic responses.…”

“…Pinkham reported that estrogen modulates cardiac afferent mediated autonomic drive ( Pinkham and Barrett, 2015 ). We demonstrated that pericardial BK injection increased venous tone, an important CO control factor, in both male and female rats ( Martin et al, 2020 ) in a sexually dimorphic manner. Accordingly, we hypothesized that activation of pericardial bradykinin-sensitive afferents would produce a sexually dimorphic cardiac output response.…”

Venoconstrictor responses to activation of bradykinin‐sensitive pericardial afferents involve the region of the hypothalamic paraventricular nucleus

“…Veins play an important role in the control of cardiovascular function by regulating venous return, cardiac output, and, therefore, arterial blood pressure. Our previous work showed that pericardial injection of bradykinin increased MCFP, an index of venous tone(Martin et al, 2020). We also reported that disinhibition of the PVN increased venous tone(Martin et al, 2006).…”

Pre-clinical safety and therapeutic efficacy of a plant-based alkaloid in a human colon cancer xenograft model

“…Institutionally supported core facilities performed comprehensive assessments of the impact of VTD on live animals. Both the Physiology Core Facility [ 50 – 53 ] and the Behavioral Core Facility [ 29 , 54 , 55 ] at the University of South Dakota have published in their respective specialties. Blood/tissues were collected, and subsequent bioanalysis was performed by collaborators at the Center for Human Toxicology at the University of Utah.…”