Date of Award

Spring 2021

Document Type

Honors Thesis

Department/Major

Basic Biomedical Science

First Advisor

Dr. Doug Martin

Second Advisor

Dr. Hong Zheng

Third Advisor

Dr. Yi-Fan Li

Keywords

Paraventricular Nucleus, CSAR, PVN, Cardiac Sympathetic Afferent Reflex, sex hormones, blood pressure control

Subject Categories

Cardiology | Internal Medicine | Pathology | Physiological Processes | Translational Medical Research

Abstract

Regulation of blood pressure is essential in bodily health. Hypertension and hypotension can be associated with varying diseases that could potentiate further disease. From this, understanding the mechanisms that regulate blood pressure is important within medicine. In my study, I will be focusing on a cardiovascular reflex that is less well understood, the cardiac sympathetic afferent reflex (CSAR). In particular, this work will examine sex differences in this reflex in overall function and in the involvement of an area of the brain called the paraventricular nucleus (PVN). We will test the hypothesis that there will be a significant difference between male and female rats in regard to BK-induced CSAR response. We predict that males will have a greater blood pressure and heart rate in response to CSAR stimuli. Alongside this, male subjects will have greater paraventricular nucleus cFos staining compared to female subjects. To approach this study, we will use a random selection of genetically similar rats. The rats were instrumented to measure blood pressure and heart rate and to allow pericardial injection of a drug (bradykinin) that is known to activate the CSAR. iv Pericardial injection of bradykinin was observed to increase mean arterial pressure (MAP) and heart rate (HR) by 24 +/- 4 mmHg and 20 +/- 6 bpm in male rats. In females, we observed an increase in MAP and HR of 18 +/- 2 mmHg and 12 +/- 4 bpm. Thus, MAP and HR responses appeared attenuated in female rats. However, these differences did not reach statistical significance. We assessed PVN involvement by immunostaining for cFos, an immediate early response gene product. We observed cFos staining in the PVN indicative of neural activation in this area in both male and female rats. The degree of immunostaining was an average of 5.2 stained cells counted on each image collected, with a minimum of 3 and a maximum of 7 cells each image. Total area of staining averaged 4.486 square units per image, with a minimum area of 2.517 and a maximum area of 6.982. Average cell area staining was 0.8616 square units per cell, with a minimum of 0.567 and a maximum of 0.997 per cell. This work has uncovered new aspects regarding the CSAR. Learning of how this mechanism relates to blood pressure control can then be helpful in understanding the blood pressure regulation in humans, possible differences between males and females. Ultimately, this may lead to more effective medications relating to blood pressure management customized to gender.

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