Renin-Angiotensin Role in Thirst: Paradoxical Enhancement of Drinking by Angiotensin Converting Enzyme Inhibitor

Lehr, David; Goldman, Howard; Casner, Paul R.

doi:10.1126/science.182.4116.1031

Cited by 87 publications

(43 citation statements)

References 18 publications

(8 reference statements)

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“…The increase in water intake has been shown by Lehr et al 20 using SQ20,881, another converting enzyme inhibitor. The increase in urinary output along with increase in Na excretion might suggest a relationship between sodium ion and hypertension; however, further studies on such parameters in twokidney models and with renin blocker (such as phospholipid) are essential.…”

Section: Discussionmentioning

confidence: 76%

Role of renin-angiotensin system in chronic renal hypertensive rats.

Sen¹,

Smeby²,

Bumpus³

et al. 1979

Hypertension

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SUMMARY The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysopbosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14.225, a potent conrerting enzyme inhibitor, and [Sar 1 , Thr*] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar', Thr* failed to lower Mood pressure. The renin inhibitor lowered plasma renin activity ( system there haVe been continued efforts to determine whether or not it is instrumental in maintaining blood pressure elevation in various forms of experimental or clinical hypertension. Interruption of the system by blocking renin, either with antibodies to renin 12 or with a • phospholipid renin inhibitor purified from kidney,' 1 * lowered blood pressure in most instances in botfOhort-(acute) and long-term (chronic) one-and two-kidney models of renal hypertensive rats. A major criticism of experiments involving either active or passive immunization to renin was the lack of homogeneity of renin used for antibody production. Use' of the lipid renin inhibitor has been limited and it remains to be determined whether or not this compound has effects in vivo other than renin blockade. Hosoki et al. 6 reported the synthesis of a renin inhibitor, 2-[4-(4-chlorophenoxy) phenoxyacetylamine]-ethyl phosphorylethanolamine (PE-104), which is an analog of the natural phospholipid renin inhibitor. PE-104 inhibits the reaction between renin and renin substrate in vitro and in vivo, and reduces the concentration of circulating angiotensin I in normotensive and renal hypertensive rats. It also lowered blood pressure in renal hypertensive rats when administered in a dose of 20 mg/kg/min.5 Turcotte et al. 9 synthesized a large series of phospholipid analogs and examined their structure-activity relationship for inhibiting renin. Of the compounds tested, eicosatetraenyl (3-aminopropyl) phosphonate (URI-73A), which is an analog of lyosphosphatidyl ethanolamine, was found to be the most potent inhibitor of renin both in vivo and in vitro. ' In recent work 7 utilizing specific angiotensin II inhibitors, the concept has been developed that in twokidney hypertensive animals, the renin-angiotensin system plays a role in maintenance of hypertension but in the one-kidney model, where the contralateral kidney has been removed, it does not. The latter is generally believed to be more volume-dependent than renin-dependent.

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Section: Discussionmentioning

confidence: 76%

Role of renin-angiotensin system in chronic renal hypertensive rats.

Sen¹,

Smeby²,

Bumpus³

et al. 1979

Hypertension

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“…Potent angiotensin-converting enzyme activity has been found in the brain. Lehr et al (1973) and Summy-Long & Severs (1974) found that the enhancement of drinking to isoprenaline or hypovolaemia was prevented if SQ 20,881 was given intracranially as well as systemically, even though drinking was not reduced below that level observed following treatment with isoprenaline alone.…”

Section: Effects Of Captopril On Drinkingmentioning

confidence: 99%

“…injections of another converting enzyme inhibitor, SQ 20,881, have also been found to increase rather than decrease drinking in response to isoprenaline, caval ligation and hypovolaemia (Lehr, Goldman & Casner, 1973;Summy-Long & Severs, 1974). Lehr et al (1973) suggested that in the presence of converting enzyme inhibitors the levels of angiotensin I in the blood become very high and angiotensin enters the brain to be converted locally to angiotensin II. Potent angiotensin-converting enzyme activity has been found in the brain.…”

Section: Effects Of Captopril On Drinkingmentioning

confidence: 99%

The renin—angiotensin system in drinking and cardiovascular responses to isoprenaline in the rat

Evered

Robinson

1981

The Journal of Physiology

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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.

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“…Ten years ago, Lehr, Goldman & Casner (1973) reported that s.c. injections of another inhibitor of CE, SQ 20,881, also enhanced drinking in response to a number of stimuli. Since SQ 20,881 is a nonapeptide, given s.c. it too probably inhibited CE in the circulation but not in the brain.…”

Section: Introductionmentioning

confidence: 99%

Increased or decreased thirst caused by inhibition of angiotensin‐converting enzyme in the rat.

Evered¹,

Robinson²

1984

The Journal of Physiology

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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.

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Renin-Angiotensin Role in Thirst: Paradoxical Enhancement of Drinking by Angiotensin Converting Enzyme Inhibitor

Cited by 87 publications

References 18 publications

Role of renin-angiotensin system in chronic renal hypertensive rats.

Role of renin-angiotensin system in chronic renal hypertensive rats.

The renin—angiotensin system in drinking and cardiovascular responses to isoprenaline in the rat

Increased or decreased thirst caused by inhibition of angiotensin‐converting enzyme in the rat.

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