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M D Evered

Publications and source records attributed to M D Evered.

30 records · Page 2Linked to original sources
PubMed1981

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

1. We investigated the role of the 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 +/- 0.9 ml water in 3 h.3. Pre-treatment with doses of captopril (0.1-1.0 mg/kg, s.c.), which inhibit conversion of angiotensin I to II in the circulation but not in the brain, dose-dependently 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 water-deprived 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.

Angiotensin II↗
PubMed1980

Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain.

In rats with permanent brain cannulas intracerebroventricular (i.c.v.) injections of 2 microgram captopril nearly abolished drinking responses elicited by i.c.v. injections of 1 mUnit hog renin, 10 pmol synthetic renin substrate or 10 pmol angiotensin I but did not reduce drinking elicited by 10 pmol angiotensin II. Inhibition of the response to precursors of angiotensin II was long-lasting (at least 2 h) and dose-dependent (20 ng-2 microgram captopril). Captopril was 3-5 times more potent than SQ 20,881 i.c.v. Subcutaneous injections of captopril in doses 0.1 to 1.0 mg/kg reduced pressor responses to intravenous injections of angiotensin I without attenuating drinking elicited by i.c.v. injections of angiotensin precursors. Higher doses of captopril, however, given subcutaneously (5-50 mg/kg) or by gavage (10 mg/kg) did not reduce drinking to i.c.v. injections of renin or angiotensin I (but not angiotensin II). We conclude that captopril inhibits angiotensin-converting enzyme activity in the brain even when given subcutaneously or by gavage in doses commonly used in the rat.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1980

Gastrin injected into the lateral hypothalamus stimulates secretion of gastric acid in rats.

Intrahypothalamic injections of 100 picomoles of pentagastrin or natural gastrin promptly increased secretion of gastric acid in conscious rats. The response was blocked by atropine and by vagotomy. The same doses, injected intravenously or into other forebrain sites, did not increase secretion, nor did intrahypothalamic injections of other peptides common to the gut and brain.

Animals↗
PubMed1978

Eledoisin, substance P and related peptides: intracranial dipsogens in the pigeon and antidipsogens in the rat.

The undecapeptide eledoisin caused vigorous and copious drinking within a minute or two of injection into the pigeon forebrain. Systemic injections of the same doses were ineffective. The relative efficacy of eledoisin and angiotensin II as dipsogens in the pigeon was similar to that of carbachol and angiotensin II in the rat. The related peptides eledoisin hexapeptide, physalaemin and substance P also caused some drinking, but they were less effective than eledoisin. In the rat none of these substances caused drinking. On the contrary eledoisin and substance P were found to depress angiotensin-induced drinking, but carbachol-induced drinking was not depressed to the same extent by these peptides. The preferential depression of angiotensin II-induced drinking resembles the effects of other vasoplegic drugs on this response in the rat, and may be related to the potent vasodilator properties of these peptides.

Angiotensin II↗
PubMed1977

Impairment in fluid ingestion in rats with lesions of the zona incerta.

Rats with lesions of the zona incerta (ZI) dorsal to the lateral hypothalamus drink as much water as controls following intracellular or extracellular dehydration but restrict their daily water intake to minimal requirements for fluid balance, suggesting a specific impairment in secondary drinking. Following water deprivation, however, rats with ZI lesions responded to changes in palatability of the water as if they were experiencing slightly greater difficulty or aversiveness in drinking than controls. The cause appears to be an impairment in the ability to lick fluids from a spout. When water was available ad libitum or when water or liquid diet were provided after water or food deprivation, rats with ZI damage were unable to obtain as much fluid per lick as controls. It is concluded that lesions in this region of the brain impair the motor act of drinking and that the subsequent reduction in the efficiency of drinking is the cause of the attenuation of excessive water intake.

Animals↗
PubMed1976

Regulatory and secondary water intake in rats with lesions of the zona incerta.

Bilateral electrolytic lesions of the zona incerta (ZI) permanently reduced daily water intake of rats by 20-30%. Lesioned rats did not differ from controls in daily food intake, body weight, hematocrit, or serum osmolality, Na+ or K+ levels. The hypodipsia was not caused by changes in water requirements or excretory function or by a nonspecific depression of behavior. Compensatory reductions in water losses maintained fluid balance. Lesioned rats drank as much water as controls in response to intracellular and extracellular dehydration, but unlike controls, appeared to restrict their daily water intake to these regulatory responses. Lesions of the ZI attenuated the ingestion of extra water observed when rats were maintained on a liquid diet adequate to meet fluid requirements, and daily water intake of lesioned but not control rats closely followed changes in water needs. It was concluded that lesions of the ZI reduce daily water intake towards minimal requirements for fluid balance by attenuating secondary drinking (drinking independent of water needs for fluid homeostasis.

Animals↗
PubMedDate not supplied

Test of a criterion for selecting intracranial doses of angiotensin receptor blockers.

Investigators using intracerebroventricular (ICV) injections of competitive antagonists of angiotensin II (Ang II) to study thirst usually select doses sufficient to block drinking to IV Ang II. We questioned whether this test truly indicates the dose needed under physiological conditions when Ang II-induced hypertension, which inhibits thirst, is not present. Rats were prepared with chronic venous and ICV cannulas, plus femoral arterial cannulas in those used to measure arterial pressure. Captopril (100 mg/kg SC) was given before all experiments to block endogenous Ang II production. The test dose of Ang II, 50 ng/kg/min IV for 1 hr, increased water intake and arterial pressure. We selected an ICV dose of saralasin (Sar1Ala8Ang II), 4 micrograms bolus and 4 micrograms/hr for 75 min, that did not stimulate drinking itself and completely blocked drinking to IV Ang II. This dose of saralasin only partially (45%) reduced drinking to the same dose of Ang II IV when arterial pressure was lowered by giving the vasodilator diazoxide (15 mg/kg IV). Diazoxide itself did not stimulate drinking. These results support our concern that the criterion normally used to select ICV doses of Ang II antagonists probably underestimates the amount needed to inhibit angiotensinergic drinking in hypovolemic or hypotensive animals.

Angiotensin Receptor Antagonists↗
PubMedDate not supplied

Water and solute balance in rats during 10 h water deprivation and rehydration.

Rats with bladder and venous cannulas were deprived of water from midnight (00:00) to 10:00. Water deprivation reduced food intake within 2 h, reducing the amount of water sequestered in the gut and the solute load to the tissues. There was little change in either urinary water loss or osmolality, but water-deprived rats excreted more Na+, K+, and Cl- than food-matched controls. The change in solute balance helped preserve osmolality and cell volume at the expense of extracellular fluid volume. When water was returned, rats quickly drank enough to restore the intracellular but not the extracellular fluid deficit. Plasma osmolality and sodium concentration fell below predeprivation values. Urine osmolality and excretion of Na+, K+, and Cl- fell rapidly after drinking. Drinking continued at a slower rate for at least 4 h, but urine flow also increased so water balance stabilized. The changes in intake and electrolyte excretion during water deprivation and rehydration illustrate the important role of changes in solute balance in fluid homeostasis.

Animals↗