Space conditions affect hormone regulation, altering heart rate, blood pressure and blood flow. These hormones are released by the suprachiasmatic nucleus (SCN) in the brain, but the mechanisms that trigger their release are not understood. Dr. Vincent Cassone is studying the signaling pathways between the SCN and the heart, and he is exploring how the pathways are altered in a simulated space environment.
Vincent Cassone, Ph.D.
Texas A&M University
This project is directed at the physiological mechanism(s) by which the mammalian circadian clock located within the hypothalamic suprachiasmatic nuclei (SCN) regulates cardiovascular function and to what extent simulated microgravity affects circadian variation in cardiovascular function. The interaction of circadian organization and other determinative factors involved in problems associated with microgravity and cardiovascular disease will be assessed through the comparative study of circadian regulation of cardiovascular function in male vs. female rats.
It is known that astronauts suffer many disruptions to normal bodily processes while in space. The most obvious of these is the redistribution of fluids in the body. This was demonstrated as early as the Mercury era, when man first ventured into space. In the microgravity environment, fluids tend to move into the chest and head, causing facial swelling and congestion. This fluid shift also reduces circulating blood volume and plasma levels of norepinephrine as well as causing a specific increased sensitivity of beta-adrenoreceptors. These changes occur due to a rise in blood pressure as perceived by the carotid baroreceptors. In Earth-based studies, bed-rest with head oriented below the feet (HDT) is believed to simulate these effects in space. HDT causes an attenuation of blood pressure rhythmicity, causing damping out of the circadian rhythm of diastolic blood pressure. Systolic blood pressure was not affected as greatly by HDT. However, HDT did not affect the circadian variation in heart rate. However, studies monitoring heart rate while in flight show that heart rate tends to increase after several days in the microgravity environment. While the circadian period of heart rate may not change, there seems to be an increase in heart rate itself.
Specific Aim #1: Determination of SCN Efferents Controlling Circadian Variations of Cardiovascular Function in Long-Term, Conscious Rats: Since it is well-known that cardiovascular responses to pressors and stress are significantly different in anaesthetized vs conscious preparations, we will characterize circadian variation in cardiovascular function in conscious freely moving rats. We will then determine whether surgical blockade of SCN efferents affects the circadian variation of heart rate, cardiac output and mean arterial pressure.
Specific Aim #2: Role of Circadian System on Daily and Circadian Variation in Regional Blood Flow: We will determine daily and circadian variations in regional blood flow measurements using 85Sr-labelled microspheres in rats whose circadian phases will be monitored independently. We will also determine whether 1) the SCN, 2) SCN efferents and 3) sympathetic innervation are required for the expression of these rhythms.
Specific Aim #3: Effects of Simulated Microgravity on Circadian Cardiovascular Rhythms: We will determine the effects of hind-limb unloading on the circadian variation in heart rate, regional blood flow and other cardiovascular variables. Based upon data obtained in Specific Aims #1 and 2, we will determine the mechanisms by which anticipated changes occur. These experiments will provide guidelines for future counter-measures in space.
Specific Aim #4: Effects of Gender on Circadian Changes in Cardiovascular Function and Their role in Responses to Microgravity: Because it is well-established that female and male astronauts experience a different set of cardiovascular responses to microgravity, we will also determine whether we can simulate those differences in our simulated microgravitational apparatus. If so, we will employ the information gained in Specific Aims #1 and 2 to provide guidelines for future countermeasures.