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Biomedical subjects

D Lehr

Publications and source records attributed to D Lehr.

At least 37 records · Page 2Linked to original sources
PubMed1976

The importance of angiotensin II formation in the CNS in angiostensin I - elicited thirst.

The drinking response produced by direct injection of angiotensin I and II into the brain of the rat, was studied, using the angiotensin blocking agents SQ-20,881 (SQ) and P-113 (Saralasin). SQ inhibits angiotensin converting enzyme, preventing formation of angiotensin II, while P-113 is an analogue and competitive inhibitor of angiotensin II. SQ blocked central angiotensin I drinking, but only when the enzyme inhibitor was injected into the ventricle. Angiotensin II induced thirst was not blocked by SQ. P-113 inhibited angiotensin I and II drinking responses in both the preoptic area of the hypothalamus and the lateral ventricle. These data indicate that conversion of angiotensin I to angiotensin II is important in angiotensin-induced drinking, although an independent action of angiotensin I on drinking can not be ruled out at this time.

Angiotensin II↗
PubMed1975

Possible role of magnesium loss in the pathogenesis of myocardial fiber necrosis.

Cellular loss of Mg is associated with uncoupling of oxydative phosphorylation and disruption of Mg-dependent intra-mitochondrial enzyme systems. The link of Mg loss and its association with intracellular Ca accumulation in the pathogenesis of myocardial fiber necrosis (MFN) has been clearly established in dietary Mg deficiency. Rapid loss of myocardial Mg has been demonstrated also in acute hypoxic states and in patients succumbing to myocardial infarction. Evidence from this laboratory indicates that loss of myocardial Mg may be a basic biochemical denominator in the development of MFN of diverse etiology, initiating a stereotyped ionic disequilibrium which encompasses loss of inorg. P and K accumulation of Na and Ca. This applies to MFN elicited by NaH2PO4 loading of parathyroidectomized rats, by injection of cardiotoxic dosages of adrenergic amines or by ligation of coronary vessels. Prevention of myocardial Ca accumulation by prior parathyroidectomy, did not interefere with emergence of MFN nor did it obviate the Mg loss and the remaining electrolyte disturbances. These parallel findings with three unrelated models of MFN do not support the view of a determinant role of CA overload. Administration of Mg salts, on the other hand, provided substantial protection against MFN induced by NaH2PO4 loading of PTX rats or by isoproterenol. The protective effect was reflected in a highly significant shift of the deranged myocardial electrolyte pattern towards normal. In rats pretreated for 3 weeks with DCA-saline, isoproterenol induced myocardial electrolyte changes including Mg depletion were associated with an enormous potentiation of the arrhythmogenic propensity of this catecholamine, resulting in almost 20,000-fold increase in its acute toxicity. Pretreatment with Mg salts or Mg-sparing drugs offered clear-out protection against arrhythmias as well as against catecholamine-induced MFN.

Animals↗
PubMed1975

Method for the production of severe ventricular dysrhythmias in small laboratory animals.

In earlier reports from this laboratory, it was shown that 3 weeks' pretreatment with desoxycorticosterone acetate (DCA) pellet implantation and saline as drinking fluid caused a nearly 20,000-fold potentiation of the acute cardiotoxicity of isoproterenol. In such animals, the beta-receptor stimulant consistently elicited severe ventricular dysrhythmias, usually leading to ventricular fibrillation (VF) and death. In the present study, a similar enhancement of isoproterenol arrhythmogenic activity after DCA-saline pretreatment was demonstrated also in the guinea pig and albino mouse. It was found, further, that isoproterenol consistently caused an alteration of the total myocardial electrolyte content in DCA-saline-treated rats, consisting of a decrease of magnesium (Mg) and potassium (K) levels and elevation of sodium (Na). In control rats, on the other hand, isoproterenol did not alter the myocardial Mg content and increased K. The emertence of cardiac irregularities and VF could be inhibited by pretreatment with antiarrhythmic drugs. On a molar basis, these agents decreased the incidence of VF in the following descending order: dl-propranolol (100), practolol (39), d-propranolol (34), sotalol (20), quinidine (8), and lidocaine (5). In the presence of any of the listed drugs, except for lidocaine, isoproterenol did not lower Mg levels and had variable effects on those of Na and K. Pretreatment with Mg gluconate was likewise effective in preventing isoproterenol-induced dysrhythmias and death. These findings demonstrate that: a) sensitization of the myocardium by DCA-saline treatment is not species-specific for the rat; b) this phenomenon can be a useful method for the screening of antiarrhythmic drugs; and c) isoproterenol-induced dysrhythmias may be associated with myocardial electrolyte alterations involving especially Mg depletion.

Animals↗
PubMed1973

Renin-angiotensin role in thirst: paradoxical enhancement of drinking by angiotensin converting enzyme inhibitor.

A competitive angiotensin converting enzyme antagonist SQ 20, 881 (SQ), was used to examine the role of the renin-angiotensin system in putative renin-dependent thirst in the albino rat. Significant enhancement of "renin-dependent" as well as renin-independent drinking was observed in the presence of peripheral SQ. Intraventricular SQ obviated this enhancement of drinking but did not affect the water intake caused by the original stimulus itself, whereas it sharply reduced drinking evoked by peripheral renin in nephrectomized rats. Prior renin depletion likewise had no influence on so-called renin-dependent thirst.

Angiotensin II↗