No abstract

To investigate the relationship between angiotensin II (ANG II) and mean arterial pressure (MAP) in the control of drinking in rats, we infused ANG II intravenously at constant rates (either 50 or 100 ng.kg-1.min-1 for 90 min) and varied MAP by intravenous injections of diazoxide (5-20 mg/kg). Rats were pretreated with captopril to block the endogenous synthesis of ANG II. When given alone, low and high doses of ANG II increased MAP approximately 30 and 50 mmHg, respectively. The low but not the high dose significantly increased water intake above control levels. Both doses caused such a large diuresis and natriuresis that the net effect was fluid loss. Reducing MAP toward normal greatly increased the drinking response to the high but not the low dose of ANG II and reduced the urinary solute and water loss to both doses. These results support the hypothesis that water intake and net fluid gain are inhibited when MAP is above normal. When MAP was reduced below normal in rats given constant infusions of ANG II the amount of water drunk and net fluid gain was proportional to the dose of ANG II but not the dose of diazoxide, the degree of hypotension, or urinary losses. This is consistent with previous reports that ANG II is essential for the drinking response to hypotension. Furthermore, it demonstrates that ANG II is not merely permissive but probably the signal controlling water intake when arterial pressure is reduced below normal.

We investigated whether the pressor response to intravenous angiotensin II (ANG II) suppresses drinking. All experiments were done on conscious water-replete rats (200-400 g) with chronic vascular cannulas. Two rates of ANG II infusion (16.7 and 100 ng/min for 90 min) were tested; captopril (0.33 mg/min) was infused simultaneously to prevent endogenous production of ANG II. Both doses of ANG II increased mean arterial pressure (MAP) by 40-50 mmHg for the duration of the infusions, but water intakes were small. The drinking response was increased as much as fivefold, however, when the pressor response was reduced by injecting either isoproterenol (0.01 or 0.1 mg/kg, sc), diazoxide (20, 30, or 75 mg/kg, sc), or minoxidil (10 mg/kg, ip) 15 min after starting the ANG II infusion. The closer MAP was returned to normal, the greater was the drinking response. Since lowering MAP also reduced urinary water losses, net fluid intake increased even more dramatically. It is unlikely that the vasodilators directly stimulated thirst in the experiments because the dose of captopril used completely blocked drinking to these agents given alone. A situation of high circulating levels of ANG II but with MAP near or below normal more closely resembles physiological conditions of dehydration. Our results demonstrate that intravenous ANG II is a very potent dipsogen under these conditions.

SUMMARY1. We have investigated the effects on water intake of subcutaneous (s.c.) injections of low (0 5 mg/kg) and high (100 mg/kg) doses of captopril, an inhibitor of angiotensin-converting enzyme (CE). Low doses block the synthesis of angiotensin II only in the circulation whereas high doses block CE in both the blood and the brain.2. The low dose of captopril enhanced drinking in response to three hypotensive drugs, isoprenaline (0-1 mg/kg, s.c.), phentolamine (5 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.), whereas the high dose of captopril abolished drinking in response to these stimuli.3. The low dose of captopril also enhanced drinking in response to histamine (0-25-50 mg/kg, intraperitoneal, i.P.), but in this case the high dose of captopril only partially reduced the drinking response.4. The low dose of captopril enhanced drinking after 24 h water deprivation but high doses had no significant effect on deprivation-induced thirst.

SUMMARY1. We investigated the role ofthe renin-angiotensin system in isoprenaline-induced drinking in the rat. Captopril, an inhibitor of angiotensin-converting enzyme, was used to block the synthesis of angiotensin II either in the circulation alone or in the brain as well.2. Subcutaneous injections of isoprenaline (0-1 mg/kg) alone caused nine rats to drink 8'4 + 09 ml water in 3 h.3. Pre-treatment with doses of captopril (0-1-10 pmg/kg, s.c.), which inhibit conversion of angiotensin I to II in the circulation but not in the brain, dosedependently enhanced the drinking response to isoprenaline. Captopril alone did not cause drinking. 4. Higher doses of captopril (5-0-100 mg/kg, s.c.), which inhibit conversion of angiotensin I to II in the brain as well as in the blood, caused dose-dependent inhibition of drinking elicited by isoprenaline.5. The highest dose of captopril tested (100 mg/kg, s.c.) completely blocked the drinking response to isoprenaline (0-1 or 0 33 mg/kg, s.c.) for at least 45 min. This inhibition was not caused by general debility of the rats; animals deprived of water (12 h) and treated with both captopril and isoprenaline drank as much as waterdeprived controls.6. We found no evidence that blocking the renin-angiotensin system inhibits drinking because it exacerbates isoprenaline-induced hypotension. After injection of isoprenaline the mean arterial pressure of nephrectomized rats or rats pre-treated with the high dose (100 mg/kg, s.c.) of captopril (which blocked drinking) was only slightly lower (5-10 mmHg) than that of rats pre-treated with the low dose (0 5 mg/kg, s.c.) of captopril (which enhanced drinking).7. Water deprivation, which caused rats treated with isoprenaline and captopril to drink, did not increase arterial pressure. Pitressin increased the arterial pressure of rats treated with isoprenaline and captopril but did not cause drinking.We conclude that the renin-angiotensin system has a direct and essential role in the drinking response to isoprenaline.