Role of Intracerebral Angiotensin Receptors in the Regulation of Vasopressin Release and the Cardiovascular System

Abstract

In order to investigate the physiological role of the brain renin-angiotensin system in the regulation of vasopressin (ADH) release, angiotensin II (Ang II, 10 ng/kg/min) or l-Sar-8-Ile-Ang II (50 ng/kg/min), an Ang II antagonist, was administered intracerebroventricularly to dogs (n = 42) anesthetized with urethane and chloralose after morphine sedation. The effects of the intravenous infusion of either 0.15 M or 2.5 MNaCl (0.1 ml/kg/min, 75 min) were also studied. In control dogs, artificial cerebrospinal fluid (ACSF) was administered at a rate of 10 µl/min for 105 min. ACSF given intracerebroventricularly plus 0.15 M NaCl given intravenously did not affect ADH release, but 2.5 MNaCl given intravenously raised the plasma ADH level in parallel with the rise in plasma osmolality. Heart rate and blood pressure did not change significantly in ACSF along with 0.15 M NaCl, but heart rate increased significantly in ACSF along with 2.5 M NaCl. Ang II along with 0.15 M NaCl significantly raised plasma ADH and decreased heart rate without any changes in blood pressure. Ang II along with 2.5 M NaCl brought about a significant rise in plasma ADH level, arterial blood pressure, heart rate, and plasma osmolality. But simultaneous application of Ang II and 2.5 M NaCl did not result in a larger rise in plasma ADH than that expected from the effects of the two stimulations given separately. Namely, Ang II did not potentiate ADH release elicited by osmotic stimulation. Ang II antagonist given intracerebroventricularly neither affected ADH release and the cardiovascular system in 0.15 M NaCl nor inhibited ADH release in response to osmotic stimulation. Ang II antagonist completely blocked the effects of Ang II. These results clearly show that Ang II given intracerebroventricularly stimulates the receptors within the brain to elicit ADH release, but does not potentiate ADH release provoked by peripheral osmotic stimulation. Ang II does not stimulate the cardiovascular system during 0.15 M NaCl challenge, but stimulates it during 2.5 MNaCl challenge.

Impaired vasopressin suppression and enhanced atrial natriuretic hormone release following an acute water load in primary aldosteronism

“…CSFosm has been reported to lag behind Posm after an acute osmotic challenge (16,17). Thirdly, an activation of the brain renin-angiotensin system (RAS) in þMCE subjects (18), in spite of a suppressed peripheral RAS, may stimulate AVP release (19,20). It is also possible that antihypertensive drugs taken by the patients in the þMCE state may have affected AVP release, although such effects have not yet been reported in patients taking calcium antagonists, or a-or b-receptor blocking agents.…”

Neuroendocrine Control of Body Fluid Metabolism

“…Hypotension causes renal renin release and leads to the formation of ANG II; binding of this hormone to AT 1 receptors in the SFO neurons promotes activation of a central angiotensinergic input that, in turn, has a predominantly excitatory effect on AVP neurons. In support of this role for ANG II, injection of ANG II or III into the SON or PVN increases magnocellular activity and AVP release into the bloodstream (28,476,578).…”

Effect on Vasopressin Release of Microinjection of Angiotensin II into the Paraventricular Nucleus of Conscious Rats

“…All of the components of the renin-an giotensin system, including angiotensin II itself, are found in the brain [10, II], Specific angiotensin II receptors have been demonstrated throughout the central nervous system [10,12,24,29,31]. It has been shown repeatedly that the injection of angiotensin II into the cerebral ventricular system stimulates vasopressin release in many species [16,28,37,48]. Finally, there have been reports suggesting the involvement of central angiotensin receptors in the osmotic control of vasopressin re lease [I, 3, 36,41,47], Although angiotensin II does not cross the blood-brain bar rier, the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) structures, which do not have a complete blood-brain barrier, are thought to contain the recep tive sites for blood-bom angiotensin II, to mediate its central actions [39].…”