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M M Robinson

Publications and source records attributed to M M Robinson.

30 records · Page 2Linked to original sources
PubMed1987

Pressor action of intravenous angiotensin II reduces drinking response in rats.

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.

Angiotensin II↗
PubMed1987

Fixation and immunofluorescent analysis of creatine kinase isozymes in embryonic skeletal muscle.

Pectoral muscles from chicken embryos of various ages were examined with immunofluorescent and radiolabeled probes for the presence of brain-type creatine kinase (B-CK), muscle-specific creatine kinase (M-CK), muscle-specific myosin heavy chain (MHC), and cycling cells. The diffusible creatine kinase isozymes were not detectable by indirect immunofluorescence after standard histological fixation of embryonic muscle. However, a fixation procedure was devised that permitted immunodetection of the creatine kinase isozymes (particularly B-CK) in embryonic tissue from all stages of development studied. B-CK, M-CK, and MHC were all detected in post-mitotic muscle cells, but only B-CK was detected in cycling cells. Correlations between these findings and in vitro observations of a deterministic muscle lineage are discussed.

Animals↗
PubMed1984

BB creatine kinase and myogenic differentiation. Immunocytochemical identification of a distinct precursor compartment in the chicken skeletal myogenic lineage.

Antisera specific for the B monomer of creatine kinase (B-CK), the M monomer of creatine kinase (M-CK), and muscle-specific myosin heavy chain (MHC) were used to investigate the biochemical characteristics of individual cells in primary myogenic cultures. Through the use of immunocytochemical techniques, in conjunction with 3H-thymidine autoradiography, it was determined that (1) all of the terminally differentiated myoblasts contained B-CK in addition to M-CK and MHC, (2) none of the cycling cells contained M-CK or MHC, (3) a fraction (7.5%) of the cycling cells contained B-CK, and (4) the cycling, B-CK positive cells divided once, and only once, and produced two terminally differentiated myoblasts. These results indicate that myogenic precursors in vitro are a phenotypically heterogeneous cell population and that the appearance of B-CK in cycling myogenic cells is a biochemical manifestation of a distinct precursor compartment in the chicken skeletal myogenic lineage.

Animals↗
PubMed1984

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

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. 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. The low dose of captopril also enhanced drinking in response to histamine (0.25-5.0 mg/kg, intraperitoneal, I.P.), but in this case the high dose of captopril only partially reduced the drinking response. The low dose of captopril enhanced drinking after 24 h water deprivation but high doses had no significant effect on deprivation-induced thirst. Hypovolaemia was produced either by injecting polyethylene glycol (30% w/v, 10 ml/kg) S.C. or by replenishing the cellular deficit in water-deprived rats with 10 ml water (by gavage). The low dose of captopril enhanced the drinking response to hypovolaemia but the high dose had no significant effect. Neither the high nor the low dose of captopril significantly affected drinking in response to cellular dehydration caused by injecting 2 M-NaCl (2 ml) I.P. or by replenishing the extracellular deficit in water-deprived rats (10 ml balanced salt solution by gavage). Nephrectomy (but not ligation of the ureters) or injections of propranolol (5 mg/kg, S.C.) to prevent renin secretion prevented the enhancement of deprivation-or serotonin-induced thirst by the low dose of captopril. The low dose of captopril did not enhance drinking in response to I.V. injections of renin (1 Goldblatt unit), or intracerebroventricular (I.C.V.) injections of angiotensin I or II. The high dose of captopril blocked drinking in response to I.V. injections of renin or I.C.V. injections of angiotensin I but did not reduce drinking in response to angiotensin II, I.C.V. These results are consistent with the hypothesis that blocking CE only in the circulation enhances drinking in response to hypotension or hypovolaemia because angiotensin I, accumulating in high concentration in the blood, enters the brain and is converted intracerebrally to angiotensin II. These findings suggest that the enhancement of drinking caused by low doses of captopril s.c. is a sensitive indicator of whether the renin- angiotensin system participates at all in the regulatory response to a particular stimulus to drink.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Effects of systemic and intracranial inhibition of angiotensin-converting enzyme on isoproterenol-induced drinking in the rat.

We have investigated the effects of separate and combined s.c. and intracerebroventricular (i.c.v.) injections of captopril, an inhibitor of angiotensin I-converting enzyme, on isoproterenol-induced thirst. Whereas s.c. injections of captopril (0.5 mg/kg) increased drinking, combined s.c. and i.c.v. (20 micrograms) injections of captopril nearly abolished drinking to isoproterenol (0.1 mg/kg s.c.). This inhibition was not caused by general debility of the rats since the same treatment did not reduce drinking to 12h water deprivation. Intracerebroventricular injection of 20 micrograms captopril alone also greatly reduced isoproterenol-induced drinking, perhaps because it leaked into the circulation; captopril i.c.v. also reduced the pressor response to i.v. injection of hog renin (0.1 Goldblatt Unit) by about 65%. These results support the hypotheses that the renin-angiotensin system participates in the stimulation of drinking by isoproterenol and that the enhancement of drinking caused by inhibition of CE only in the circulation is the result of increased synthesis of angiotensin II in the brain.

Angiotensin II↗
PubMed1983

Effects of captopril on salt appetite in sodium-replete rats and rats treated with desoxycorticosterone acetate (DOCA).

Captopril (30 mg/kg daily by gavage), an orally active inhibitor of angiotensin-converting enzyme, reduced the intake of 0.15 M NaCl in rats treated with desoxycorticosterone acetate (2.5 mg/day S.C.). However, this is probably not a specific effect on salt appetite as captopril (30 or 60 mg/kg daily) did not reduce the intake of less palatable 0.5 M NaCl in desoxycorticosterone acetate-treated rats (1 or 2.5 mg daily). In contrast, captopril given alone (30 or 60 mg/kg daily) consistently caused a 3- to 5-fold increase in intake of 0.5 M NaCl that usually began on the 1st day and persisted until treatment stopped (1-3 weeks). Sodium intake and sodium excretion increased concomitantly, but the stimulation of salt appetite occurred even in the absence of sodium depletion. Also, the effect on salt appetite was specific; captopril did not increase the intake of 0.5 M KCl or 0.03 M sucrose. This potent and specific stimulation of sodium intake by oral treatment with an inhibitor of the renin-angiotensin system may be caused by a paradoxical increase in the synthesis of angiotensin II in the brain.

Animals↗
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

Quantitation of the anticonvulsant cinromide (3-bromo-N-ethylcinnamamide) and its major plasma metabolites by thin-layer chromatography.

A quantitative thin-layer chromatography (TLC) procedure is described for the analysis of cinromide (3-bromo-N-ethylcinnamamide) and its two major metabolites, 3-bromocinnamamide and 3-bromocinnamic acid in plasma of the dog. These compounds were recovered from acidified plasma by extraction into benzene with a recovery of 95 +/- 5%. All three compounds were quantitated directly on a TLC plate by ultraviolet absorbance densitometry at 270 nm. The linear dynamic range for the quantitation of the compounds on a TLC plate ranged between 10 and 1000 ng. The complete procedure is useful in the working range of 50 ng/ml to 100 microgram/ml of plasma with a coefficient of variability of about 10%. Specificity of the method for parent drug and each of its plasma metabolites was confirmed by high-performance liquid chromatography. The method was used to determine the pharmacokinetics of cinromide and its two major plasma metabolites in dogs following a single oral dose of the drug.

Animals↗
PubMedDate not supplied

Improved methods for the diagnosis of African trypanosomosis.

The diagnosis of trypanosomosis in animals with low parasitaemia is hampered by low diagnostic sensitivity of traditional detection methods. An immunodiagnostic method based on a direct sandwich enzyme-linked immunosorbent assay (ELISA), using monoclonal antibodies, has been examined in a number of African laboratories for its suitability for monitoring tsetse control and eradication programmes. Generally, the direct sandwich ELISAs for the detection of trypanosomal antigens in serum samples have proved to be unsatisfactory with respect to diagnostic sensitivity when compared with traditional parasitological methods such as the dark ground/phase contrast buffy-coat technique. Consequently, antigen-detection systems exploiting various other direct, indirect and sandwich ELISA systems and sets of reagents are being developed to improve diagnosis. In addition, an existing indirect ELISA for the detection of antibodies has been improved and is being evaluated in the field in order to detect cattle that are or have been recently infected with trypanosomes. Developments and advantages of other diagnostic techniques, such as dip-stick assay and tests based on the polymerase chain reaction are also considered.

Animals↗