Ryuto Hirasawa

Central interaction between endothelin and brain natriuretic peptide on pressor and hormonal responses

Interaction between intracerebroventricular (i.c.v.) administration of endothelin (ET) and brain natriuretic peptide (BNP) on pressor and hormonal responses was examined in unanesthetized, freely moving rats. I.c.v. administered ET (5, 20 or 40 pmol/2 microliters) dose-dependently increased arterial pressure. Plasma catecholamine levels were elevated by 40 pmol of ET, and plasma ACTH level was also elevated by centrally administered ET in a dose-dependent manner. I.c.v. administration of BNP (0.2, 1 nmol/3 microliters) dose-dependently attenuated central ET (40 pmol/2 microliter)-induced pressor response, plasma catecholamine and ACTH secretion. These results indicate that ET may be one of the neuropeptides which stimulate both sympathetic nervous system and hypothalamo-pituitary-adrenal axis, and that BNP and ET interact in the central nervous system (CNS) to regulate cardiovascular and hormonal functions. Furthermore, these results raise a possibility that BNP antagonizes the effect of not only angiotensin II but also other neuropeptides in the CNS.

Central interaction between endothelin and brain natriuretic peptide on vasopressin secretion.

Objective: To examine the interaction between i.c.v. administration of endothelin and brain natriuretic peptide (BNP) on vasopressin (AVP) secretion in unanesthetized, freely moving rats. Methods: i.c.v. cannulation and femoral artery catheterization were performed 7-8 days and 2 days before the experiment, respectively. Endothelin and BNP were injected into the third ventricle through the guide cannula. One millilitre of blood was collected for AVP measurement 30 min before and 10 min after i.c.v. injection. Results: Central administration of endothelin (20 or 40 pmol/2 (µl) dose-dependently evoked the elevation of plasma AVP levels. Preinjection of BNP (0.2 or 1 nmol/3 µl, i.c.v.) dose-dependently attenuated central endothelin (40 pmol/2 µl)-induced plasma AVP secretion. Conclusions: We have already reported that BNP attenuated central endothelin-induced pressor response and plasma catecholamine secretion. Taken together, the results indicate that BNP attenuated central endothelin-induced pressor response, at least partially, by suppressing sympathetic nervous system activation and plasma AVP secretion.

Role of central angiotensinergic mechanism in shaking stress-induced ACTH and catecholamine secretion

The role of central angiotensin II (AII) in the shaking stress-induced adrenocorticotropic hormone (ACTH), plasma catecholamine secretion and pressor response were investigated using conscious rats. We also studied whether or not vasopressin (VP) is involved in the shaking stress-induced pressor response. The shaking stress caused significant elevations in plasma ACTH, catecholamine, and systolic blood pressure. Intra-third ventricular administration of the AII antagonist, Sar1, Ile8-angiotensin II (saralasin) significantly attenuated pressor response and plasma noradrenaline elevation but not plasma ACTH elevation. Pretreatment with the vascular-type VP receptor (V1) antagonist, d(CH2)5Tyr(Me)AVP, did not attenuate pressor response nor plasma catecholamine elevation. These results indicate that the central angiotensinergic pathway at least partly mediates the shaking stress-induced activation of the sympathetic nervous system without VP involvement, and that central AII does not mediate the ACTH secretion evoked by shaking stress.

Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, and plasma levels of CRH, ACTH and cortisol were determined in samples taken simultaneously from 28 patients with dementia including senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID), dementia following a cerebrovascular accident (CVD), and the borderline-to-normal state. CRH levels in CSF were significantly reduced in patients with SDAT and CVD, but not in those with MID, as compared with the borderline cases. ACTH levels in CSF were significantly reduced in the patients with SDAT compared to those with MID. Reduced CRH levels in CSF were found in the patients who showed severe dementia and poor activities of daily living (ADL). Plasma levels of CRH, ACTH and cortisol were normal and were not significantly different among the four groups of patients. CRH levels in CSF were positively correlated with ACTH levels in CSF, but not with the levels of plasma CRH, ACTH or cortisol. Plasma CRH levels were positively correlated with plasma ACTH levels. These results suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) CSF CRH is correlated with the severity of dementia and ADL; 3) the levels of CRH in CSF and plasma are independent, and 4) the plasma CRH reflects, at least in part, the activity of the hypothalamic CRH regulating the secretion of pituitary ACTH.

Corticotrophin‐Releasing Factor Antagonist [alpha helical CRF(9–41)] Blocks Central Noradrenaline‐lnduced ACTH Secretion

Plasma ACTH increased after an intra‐third ventricular administration of noradrenaline (NA). An iv corticotrophin‐releasing factor (CRF) antagonist [alpha‐helical CRF(9–41)] injection did not affect ACTH secretion by itself, whereas it significantly reduced NA‐induced ACTH secretion. These results suggest that NA centrally stimulated ACTH secretion and that endogenous CRF is involved in this ACTH secretion.