| 研究実績の概要 |
Baroreflex activation therapy (BAT) uses electrical stimulation of baroreceptors to reduce arterial pressure (AP) in resistant hypertensive patients. However, the electrical stimulation of the two types of baroreceptor afferents, myelinated (A-fiber) and unmyelinated (C-fiber), may have significantly different outcomes. We hypothesize that the central processing of A-fiber and C-fiber baroreceptors are affected differently during the development of hypertension and during stimulation in BAT. To understand the role of C-fiber baroreceptor pathway, a stimulation electrode for the left aortic depressor nerve (ADN) was implanted in rats, and the effect of ADN stimulation was chronically monitored. After confirming the stimulation-induced hypotensive response, resiniferatoxin was administered intraperitoneally to block C-fibers. The successful blockade of C-fiber afferents was confirmed by the absence of blinking response to eye drop of a small amount of capsaicin. The blockade of systemic C-fiber afferents was expected to elevate AP in normotensive rats, however, AP did not increase after the administration of resiniferatoxin. It was speculated that the TRPV1 receptors participate in drinking behavior, and resiniferatoxin may have caused dehydration of animals due to the loss of thirst. In acute experiments, we have confirmed that the C-fiber afferents are important for baroreflex-mediated sustained AP regulation, and the function of C-fiber afferents is impaired in spontaneously hypertensive rats. Therefore, we are planning to perform chronic ADN stimulation in SHR next year.
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Chronic implantation of the stimulation electrode for the aortic depressor nerve, and the blockade of C-fiber afferents by intraperitoneal administration of resiniferatoxin were successful. However, the blockade of C-fiber afferents did not chronically elevate arterial pressure in normotensive rats. Meanwhile, we performed an acute baroreflex study to compare the function of A- and C-fiber afferents in normotensive rats and spontaneously hypertensive rats.
|
| 今後の研究の推進方策 |
As described in the progress status, because resiniferatoxin did not increase arterial pressure in normotensive rats, we are now planning to implant the stimulation electrode in spontaneously hypertensive rats and examine the baroreflex responses. Other models of hypertension such as Dahl salt sensitive rats will be examined for the relative roles of A- and C-fiber baroreceptors.
|
