Microinjections of Angiotensin II into the Supraoptic and Paraventricular Nuclei Produce Potent Antidiureses by Vasopressin Release Mediated through Adrenergic and Angiotensin Receptors

Abstract

ABSTRACT-We investigated the effects of angiotensin II (Ang II), microinjected into the supraoptic (SON) and paraventricular (PVN) nuclei of rats, on the urine outflow rate and underlying mechanisms. Ang II produced antidiuretic effects in a dose-dependent manner with ED50 values of 0.1 and 0.05 nmol in the SON and PVN, respectively. [Sar', Ile8]Ang II at 0.1 nmol diminished the Ang II (0.5 nmol)-induced anti diureses in the SON more markedly than in the PVN. A high dose of [Sar', Ile8]Ang II, 1 nmol, completely inhibited the effects in both the nuclei. In addition, the Ang II (1 nmol)-induced antidiuretic effects were par tially inhibited by phenoxybenzamine (80 nmol) in the SON and by phenoxybenzamine, timolol (100 nmol) and propranolol (100 nmol) in the PVN. The microinjection of Ang II (1 nmol) into both the nuclei, after pretreatment with a vasopressin V1V2-antagonist, d(CH2)5-u-Tyr(Et)VAVP (i.v.), significantly increased the urine outflow rate. These findings suggest that 1) Two mechanisms account for the Ang II receptor mediated antidiureses resulting from an increase in vasopressin release: direct stimulation on vasopressin containing neurons and indirect stimulation on them through a-adrenoceptors in the SON and a and ã drenoceptors in the PVN; 2) The Ang II-induced antidiuretic effect in the SON is slightly less potent than that in the PVN; and 3) Ang II receptors in the nuclei may possibly produce the diureses through mecha nisms that are not presently understood.

Expressions of per1 Clock Gene and Genes of Signaling Peptides Vasopressin, Vasoactive Intestinal Peptide, and Oxytocin in the Suprachiasmatic and Paraventricular Nuclei of Hypertensive TGR[mREN2]27 Rats

“…Moreover, posttranscriptional regulation of AVP concentrations in the lower brain stem, in comparison with the posterior pituitary, has already been demonstrated (Moriguchi et al 1994). Microinjections of angiotensin II (Ang), a final mediator of the RAS, into the PVN have been shown to elicit dose-dependent AVP secretion (Tsushima et al 1994), and intracerebroventricular administration of Ang increased avp mRNA expression (Zhang et al 2009). Vasopressin release is stimulated by Ang also in the TGR rats (Nishioka et al 1999).…”

Angiotensinergic Regulation of Autonomic and Neuroendocrine Outputs: Critical Roles for the Subfornical Organ and Paraventricular Nucleus

“…increases in blood pressure and heart rate) were also inhibited by systemic pretreatment with losartan while cardiovascular changes elicited by PVN stimulation were unaffected [43]. Direct administration of angiotensin II into the PVN has also been reported to result in increases in blood pressure and secretion of a number of different hormones [43,44,45]. Collectively, these studies support the conclusion that angiotensin II is utilized by SFO neurons projecting to PVN as an excitatory neurotransmitter which plays important roles in modulating the excitability of neuroendocrine and pre-autonomic neurons of the PVN.…”

Age-dependent cardiovascular, renal and endocrine responses to furosemide in conscious lambs

“…Another possible explanation lies with the greater renin response to furosemide measured in 1-week-old lambs, which could stimulate the release of arginine vasopressin independently of any effects of plasma osmolality, vascular volume or MAP through the direct effects of angiotensin II in the central nervous system. 35 Yet, this would not explain why there was no increase in arginine vasopressin measured in older animals, in which there was also a significant renin response to furosemide, albeit a lesser response than that measured in the younger animals. The mechanism underlying the age-dependent arginine vasopressin response to furosemide warrants further investigation.…”

“…Therefore, it is somewhat surprising that the arginine vasopressin response to high‐dose furosemide was quite marked in lambs aged 1 week, whereas no effect was seen in lambs aged 6 weeks. Another possible explanation lies with the greater renin response to furosemide measured in 1‐week‐old lambs, which could stimulate the release of arginine vasopressin independently of any effects of plasma osmolality, vascular volume or MAP through the direct effects of angiotensin II in the central nervous system 35 . Yet, this would not explain why there was no increase in arginine vasopressin measured in older animals, in which there was also a significant renin response to furosemide, albeit a lesser response than that measured in the younger animals.…”