Effect of hyperkalemia on insulin secretion

Summary The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68±0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p<0.05). We conclude that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Effect of hyperkalemia on insulin secretion

The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68 +/- 0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration

Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of “mature” and “immature” cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.     

Independence of circulating insulin levels of the increased glucose turnover in shivering dogs

Summary In dogs, selective insulin deficiency induced by simultaneous somatostatin and glucagon infusion does not alter the high rate of glucose utilization provoked by acute cold exposure. However, both in resting and in shivering dogs, lowering of plasma insulin decreases plasma glucose metabolic clearance significantly.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia.

Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2.     

Hematocrit as an index of changes in plasma volume in conscious dogs.

Hematocrit (HCT) measurements were made in intact and splenectomized conscious dogs to determine if observed decreases in HCT were produced by plasma volume expansion or splenic sequestration of erythrocytes. We found that in conscious dogs HCT is a poor indicator of changes in plasma volume.     

Independence of circulating insulin levels of the increased glucose turnover in shivering dogs

In dogs, selective insulin deficiency induced by simultaneous somatostatin and glucagon infusion does not alter the high rate of glucose utilization provoked by acute cold exposure. However, both in resting and in shivering dogs, lowering of plasma insulin decreases plasma glucose metabolic clearance significantly.     

Presence of sodium transport inhibiting factor in dog plasma during volume expansion

Summary Plasma dialysates from volume-expanded dogs (E) were compared directly to dialysates from the same dogs when hydropenic. In a double-blind study, E caused relative inhibition of short-circuit current in toad urinary bladder. We therefore confirm the presence of a sodium transport inhibiting factor in plasma of volume-expanded dogs.Acknowledgments. This study was supported by the Philadelphia Veterans Administration Hospital (103.6M). We would like to thank the laboratory of Dr V. Buckalew at Bowman Gray School of Medicine, Winston-Salem, North-Carolina, for preparation of plasma dialysates; G. Huber and E. Fink for technical assistance and K. Conrad for secretarial assistance.     

Presence of sodium transport inhibiting factor in dog plasma during volume expansion.

Plasma dialysates from volume-expanded dogs (E) were compared directly to dialysates from the same dogs when hydropenic. In a double-blind study, E caused relative inhibition of short-circuit current in toad urinary bladder. We therefore confirm the presence of a sodium transport inhibiting factor in plasma of volume-expanded dogs.     

Hematocrit as an index of changes in plasma volume in conscious dogs

Summary Hematocrit (HCT) measurements were made in intact and splenectomized conscious dogs to determine if observed decreases in HCT were produced by plasma volume expansion or splenic sequestration of erythrocytes. We found that in conscious dogs HCT is a poor indicator of changes in plasma volume.Supported by National Institutes of Health grant No. HL 13427.I.Z. ist the recipient of an Established Investigator Award from the American Heart Association.Acknowledgment. The authors wish to thank Mary Anne Richards for her technical assistance.     

Directional non-uniformity of pulsatile intramyocardial pressure

Summary A method using piezoelectric ceramics was newly devised which permitted measurements of intramyocardial pressure. In open-chest dogs, a directional non-uniformity of the intramyocardial pressure was observed, which may be attributable to the variation in the myocardial fibre orientation.     

Directional non-uniformity of pulsatile intramyocardial pressure.

A method using piezoelectric ceramics was newly devised which permitted measurements of intramyocardial pressure. In open-chest dogs, a directional non-uniformity of the intramyocardial pressure was observed, which may be attributable to the variation in the myocardial fibre orientation.     

Tolerance to cold and glucose homeostasis in adrenal demedullated dogs

Summary The rise in O₂ consumption and in glucose turnover, induced by acute cold exposure is not suppressed by adrenal demedullation in dogs. However, both at neutral and cold ambient temperature, the mean plasma glucose concentrations are higher in normal (N) than in adrenal-demedullated dogs (ADMX). In the cold, the fall in rectal temperature is larger in ADMX than in N dogs.This work was supported by a grant from Université Claude Bernard (U.E.R. Lyon Nord and U.E.R. Biologie Humaine).The authors thank D. Rougier and G. Dallevet for their excellent technical assistance and A. Brillant for secreterial assistance.     

Occurrence of inhibitory histamine H2-receptors in isolated pulmonary blood vessels of dogs and rats

Summary Isolated, helically cut strips of pulmonary arteries and veins of dogs, and pulmonary arteries of rats, precontracted with norepinephrine or 5-HT exhibited potent concentration-dependent relaxations to impromidine and dimaprit (histamine H₂-agonists). The occurrence of inhibitory histamine H₂-receptors in the pulmonary vasculature could play a modulatory role in hypoxic pulmonary vasoconstriction.Supported by research grants NHLBI-18002, NHLBI-18015 and DA-02339 from the USPHS. We are grateful to Dr D.D.A. Owen of Smith, Kline & French Ltd, England for the generous supply of dimaprit and impromidine. Requests for reprints should be addressed to B.M. Altura.     

The effect of endotoxin on plasma α-aminoisobutyric acid

Summary The i.v. injection of bacterial endotoxin into dogs was found to cause a rapid increase in plasma levels of infused -aminoisobutyric acid. The findings suggest that nonmetabolic factors (tissue uptake, fluid shifts) influence amino acid distribution during endotoxemia.This investigation was supported in part by the Office of Naval Research, Contract N0001476CO132. R.E.K., Postdoctoral Fellow, supported by HL07090. Address correspondence to J.J.S.     

The time course of plasma enzyme changes accompanying skeletal muscle stimulation

Summary 30 min electrical stimulation of hind limb skeletal muscle in nembutal anaesthetised dogs was accompanied by increases in arterial haematocrit, plasma GOT and plasma LDH, which were almost completed within the first 10 min of stimulation. This fast response indicated that a rapid change in either the entry and/or clearance of enzyme from the plasma must have occurred.     

Ultrastructural localisation of substance P and choline acetyltransferase in endothelial cells of rat coronary artery and release of substance P and acetylcholine during hypoxia

Substance P and choline acetyltransferase have been localised in a small proportion of endothelial cells of rat coronary arteries using electron microscopic immunocytochemistry. During a hypoxic period of 1 min, coronary vasodilatation was produced in the Langendorff heart preparation and increased levels of substance P and acetylcholine were released into the perfusate. The possibility that these substances are released from endothelial cells during hypoxia and contribute to the hyperaemic response is discussed.     

Ultrastructural localisation of substance P and choline acetyltransferase in endothelial cells of rat coronary artery and release of substance P and acetylcholine during hypoxia

Substance P and choline acetyltransferase have been localised in a small proportion of endothelial cells of rat coronary arteries using electron microscopic immunocytochemistry. During a hypoxic period of 1 min, coronary vasodilatation was produced in the Langendorff heart preparation and increased levels of substance P and acetylcholine were released into the perfusate. The possibility that these substances are released from endothelial cells during hypoxia and contribute to the hyperaemic response is discussed.     

Effect of ambient cold on urine concentration by the intact and denervated dog kidney

Summary In dogs transferred from room temperature to a low temperature of 1±(SD) 3.5°C, the plasma norepinephrine (NE) level increased significantly. Urine concentration decreased in the cold, in the intact and similarly in the chronically denervated kidney. After return to a warm environment urine concentration improved in both kidneys while plasma NE remained elevated. The data speak against an essential role of the renal nerves in the adaptation of renal function to ambient cold.Acknowledgments. We are greatly indebted to Dr J. Kurkus and Dr R. Gellert who performed the operations of surgical bladder division, and to Mrs W. Radziszewska for determination of plasma norepinephrine. The study was supported within the national research problem No. 10.4.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia

Summary Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N₂, 12% O₂ and 4% CO₂. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p<0.01) and a decrease in cyclic GMP (p<0.05) as compared to hearts perfused for 60 min with media gassed with 96% O₂, 4% CO₂.Acknowledgment. We gratefully acknowledge the excellent technical assistance provided by Mrs Inger O. Boggs and Miss Patricia C. Hannigan. This work was supported in part by U. S. Public Health Service grant HL 14661 from the National Heart and Lung Institute, and by a grant from the Central Ohio Heart Chapter.