saralasin and Dehydration

This report examines the importance of bladder volume in regulating cutaneous water uptake (Jv, cm3.cm-2.s-1 x 10(-7)) across the ventral pelvic patch and examines the role of angiotensin II (ANG II) and circulation as the regulatory mechanism. Jv in empty-bladder Bufo marinus (bladder volume 3.89 +/- 1.49%, n = 7) was 1,671 +/- 68 (n = 7). Injection of Ringer solution into the bladder (12.8 +/- 2.2%, n = 7) decreased Jv to 1,025 +/- 202 (n = 7). ANG II injected into toads with filled bladders increased Jv in a dose-dependent manner. At 5 micrograms/100 g toad Jv increased by 136 +/- 63 (n = 6), at 50 micrograms/100 g toad by 432 +/- 82 (n = 7), and at 200 micrograms/100 g toad by 620 +/- 142 (n = 5). Saralasin (200 micrograms/100 g toad) completely inhibited the response to ANG II (50 micrograms/100 g toad) and at 1 mg/100 g toad decreased Jv in empty-bladder toads. These experiments indicate that 1) bladder volume participates in the regulation of Jv in the ventral pelvic patch; 2) ANG II increases the Jv in toads with full bladders; 3) saralasin inhibits the high Jv in empty bladder toads; 4) the high Jv, associated with an empty bladder, requires an intact circulation to be maintained; 5) without an intact circulation, the high water flow associated with an empty bladder causes the Na+ content of the tissue in the ventral patch to be reduced; and 6) ANG II causes only a minimal increases in water permeability in the isolated pelvic patch skin.

Topics: Angiotensin II; Animals; Bufo marinus; Dehydration; Drinking; Injections; Pelvis; Regional Blood Flow; Saralasin; Skin; Sodium; Urinary Bladder; Water

Uncertainty exists as to whether endogenous angiotensin activates brain mechanisms controlling vasopressin (AVP) secretion during dehydration. We injected various doses of saralasin into a lateral cerebroventricle (IVT) of conscious, male rats deprived of water for 48 h and killed them at different times. The concentration of AVP in the plasma (p[AVP]), measured by radioimmunoassay, was unaffected by saralasin. IVT pretreatment with 1-Sar-8-Ile-angiotensin II blocked maximal AVP release by IVT angiotensin, but this pretreatment did not reduce p[AVP] after 24, 48 or 72 h water deprivation. A 3-hour continuous IVT infusion of CSF or saralasin (10 micrograms/h) into 48-hour water-deprived rats revealed equivalent p[AVP] and urine volumes. When the infusions were continued for 3 h more with water available, control and saralasin-treated rats: (a) drank at similar rates, (b) excreted similar amounts of urine, and (c) reduced their p[AVP] levels to the same extent. IVT saralasin did not affect p[AVP] of rats dehydrated with hypertonic NaCl. Combined IVT saralasin and atropine reduced p[AVP] of 48-hour water deprived rats about 30% (p less than 0.05). We conclude that redundancy exists for sensing, integrating and releasing vasopressin in dehydrated rats.

Topics: 1-Sarcosine-8-Isoleucine Angiotensin II; Animals; Atropine; Dehydration; Drinking Behavior; Injections, Intraventricular; Male; Radioimmunoassay; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Saralasin; Vasopressins; Water Deprivation

Mildly dehydrated conscious Merino ewes were infused with vasopressin (AVP) at 5 mu x min-1 alone and simultaneously with the angiotensin II receptor blocker sar1ala8-angiotensin II (saralasin) at 15 micrograms x min-1. AVP was slightly pressor and produced an increase in the calculated total peripheral resistance, and an increase in glomerular filtration rate, urine flow and electrolyte excretion, without a change in total renal plasma flow. These results indicate renal efferent arteriolar vasoconstriction as well as other non-renal vasoconstriction. Saralasin infusion checked the rise in total peripheral resistance (which continued to increase after saralasin withdrawal), but caused a marked increase in renal vascular resistance resulting in a decrease in renal plasma flow and to a lesser extent in glomerular filtration rate. These results suggest that saralasin was acting as an angiotensin II agonist in the kidney, but as an antagonist elsewhere. Deductions from previous experiments in the literature of the renal function of angiotensin II, based on its supposed inhibition by saralasin, may not be justified.

Topics: Angiotensin II; Animals; Dehydration; Female; Kidney; Saralasin; Sheep; Vasopressins

Central effects of dehydration are stimulated by osmotic stimuli, the reduced input of volume receptors, and angiotensin II. The subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT) have become accepted as putative receptor sites for angiotensin II in the brain. The exact quantitative relationship between the hours of water deprivation and the amount of angiotensin generated peripherally and whether that amount is sufficient to induce thirst centrally have not been established, but there is no question that when animals are dehydrated their angiotensin levels rise and the animals are thirsty. Attempts to block centrally the contribution of angiotensin II to thirst have been variable and cholinergic inputs have to be blocked at the same time. Various stimuli for thirst interact in a parallel fashion, and when one stimulus is blocked the other stimuli are still effective. Plasma angiotensin II may induce natural thirst, but how it enters the brain still remains to be explained. Although the SFO and OVLT have no blood-brain barrier, the blood supply to these organs acts as a limited perfusion system whereby blood-borne proteins cannot diffuse far from the capillary bed. A second set of receptors is found on the ventricular surface of the OVLT, as shown by fluorescence labeled angiotensin II. The connection between the SFO and OVLT was cut by discrete knife cuts. Drinking to angiotensin II intraventricularly was not significantly altered but the pressor response was reduced by 50%. These results can be explained by a circuit for drinking passing down below the level of the knife cut and a separate pressor pathway passing dorsally through the area that was cut by the knife. Thirst and pressor neural circuits beginning with angiotensin receptors could explain some of the data accumulated with the AV3V syndrome that occurs when the OVLT and nucleus medianas are destroyed.

Topics: Angiotensin II; Animals; Atropine; Blood Pressure; Body Fluids; Dehydration; Dogs; Drinking; Neurosecretory Systems; Rats; Receptors, Angiotensin; Receptors, Cell Surface; Renin-Angiotensin System; Saralasin; Subfornical Organ; Thirst; Water-Electrolyte Balance

Saralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 micrograms . min-1 into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenous angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.

Topics: Angiotensin II; Animals; Dehydration; Female; Glomerular Filtration Rate; Hemodynamics; Kidney; Saralasin; Sheep; Urodynamics

The effects of intraventricular injection of Sar1-Ala8-angiotensin II (A specific antagonist of angiotensin II) on the plasma vasopressin level increased by intraventricular injection of angiotensin II and by water deprivation (46 h) were examined in conscious male rats with an indwelling cannula in the third cerebral ventricle. Blood samplings were made by decapitation and the plasma level of vasopressin was determined by radioimmunoassay. Twenty-five, 50 or 100 ng of angiotensin II produced significant (P less than 0.05) increase in plasma vasopressin level 90 sec after the injection. The effect of 50 ng of angiotensin II was inhibited significantly (P less than 0.05) at least with 100 ng of Sar1-Ala8-angiotensin II given 2 min before the injection of angiotensin II. The dehydrated rats to which 1000 ng of Sar1-Ala8-angiotensin II was given 5 min before the decapitation showed the significantly (P less than 0.05) lower median plasma vasopressin level than that of the dehydrated controls. No significant difference in plasma osmolality was noted between them. These results suggest that the plasma vasopressin response to intraventricular angiotensin II is produced via angiotensin II receptors in the brain and that Sar1-Ala8-angiotensin II inhibits the effect of endogenous angiotensin II on plasma vasopressin level under dehydration.

Topics: Angiotensin II; Animals; Dehydration; Injections, Intraventricular; Male; Rats; Saralasin; Vasopressins

Blood pressure effects of angiotensin II antagonists were studied in sham-operated and baroreceptor-denervated rabbits in the normal water-replete state or after 6 days of water deprivation (dehydrated). Experiments were performed in awake rabbits. Dehydrated rabbits had significantly higher plasma sodium concentrations, hematocrits, and plasma renin activities, but lower plasma potassium concentrations and body weights than water-replete rabbits. Administration of angiotensin II antagonists caused a significant decrease in mean arterial pressure in dehydrated rabbits (-16 mmHg in sham-dehydrated and -19 mmHg in denervated-dehydrated) but not in water-replete ones, whether the baroreceptor reflexes were intact or not (-1 mmHg in sham replete and -4 mmHg in denervated replete). The open-loop feedback gain of the renin-angiotensin system in blood pressure control was calculated as -1.6. The results demonstrate an important role of angiotensin II in blood pressure regulation during the high-renin, dehydrated state, but not during the normal renin, water-replete state. Abolishment of baroreceptor reflexes did not unmask an important role of normal levels of angiotensin II in blood pressure regulation.

Topics: Angiotensin II; Animals; Blood Pressure; Dehydration; Denervation; Extracellular Space; Feedback; Homeostasis; Pressoreceptors; Rabbits; Reflex; Renin; Saralasin; Sodium; Water Deprivation