Vascular effects of raising local arterial concentration of pentagastrin (2-1,500ng/ml), secretin (0.2-150mU/ml), and cholecystokinin (0.2-150mU/ml) in the duodenum, jejunum, heart, kidney, forelimb, spleen, and the skin and muscle of the forelimb were studied in 54 anesthetized dogs. Secretin produced similar vasodilation in all organs. The minimal increment in local blood secretin concentration for vasodilation ("concentration requirement") was between 7 and 32 mU/ml. Pentagastrin produced vasodilation only in the duodenum and jejunum and the concentration requirement was between 25 and 50 ng/ml. Cholecystokinin did not affect vascular resistance of the forelimb, skin, or muscle. In the heart, kidney, and spleen, cholecystokinin produced vasodilation but the concentration requirement was above 21-33 mU/ml. In contrast, vasodilation in the duodenum and jejunum appeared when cholecystokinin concentration was increased by only 2.5 mU/ml. Furthermore, almost all its vasodilating effect occurred below an increment of 10 mU/ml. Comparison of our data with the reported cardiovascular adjustments and blood concentration of gastrointestinal hormones following a meal suggests that cholecystokinin may contribute to postprandial intestinal hyperemia.
SUMMARY We have investigated, in isolated, perfused, spontaneously beating guinea pig hearts, the influence of perfusate pH on the coronary vasodilation produced by exogenous adenosine and on the inhibition of adenosine vasodilation by theophylline. Perfusate pH 7.20 and 6.89, produced by increasing Pco 2 , reduced the concentration at which adenosine produced a response. Furthermore, the flow increment in response to higher adenosine concentrations was greater at pH 6.89 and less at pH 7.69 than at pH 7.42. The flow responses to alterations in pH was greater in the presence of adenosine (5 x 10 7 M) than in its absence. Theophylline, in amounts which by themselves were without effect on coronary flow, partially inhibited coronary vasodilation caused by adenosine both at pH 7.43 and 7.20. Our findings indicate that the coronary vasodilation produced by adenosine is pH sensitive but attenuation of this dilation by theophylline is not, at the values of pH tested. We conclude that theophylline's inability to regularly attenuate reactive hyperemia might be related to enhanced adenosine dilation caused by increased tissue hydrogen ion activity. Furthermore, the hydrogen ion might participate in coronary flow regulation in part via this interaction with adenosine.THE MAJOR objection to the adenosine hypothesis for the metabolic regulation of coronary blood flow is that theophylline, a competitive inhibitor of exogenous adenosine vasodilation, 1 has little effect on coronary hypoxic or reactive hyperemia, 2 " 5 although slight attenuation has been reported in the case of reactive hyperemia." These findings, however, are not necessarily incompatible with the adenosine hypothesis; it is possible (1) that the concentration of adenosine in the interstitial fluid during ischemia/hypoxia exceeds that which can be effectively blocked by theophylline, (2) that increased interstitial hydrogen ion activity enhances the vasodilator capacity of adenosine, and (3) that increased interstitial hydrogen ion activity reduced the ability of theophylline to inhibit adenosine vasodilation. We have investigated the latter two possibilities in the isolated guinea pig heart. MethodsThe modified Langendorff preparation described by Bunger et al. 7 was used in all experiments. Hearts from 300-to 500-g Hartley strain guinea pigs (Cannaught Laboratories) of either sex were isolated and perfused at a pressure of 65 cm H 2 O. A period of 2 to 3 minutes elapsed between the time the pigs were killed and the hearts cannulated. The perfusing fluid was a Krebs-Ringer bicarbonate solution containing (in mti): glucose, 5.5; pyruvate, 2.0; NaCI, 127.5; K.C1, 4.7; CaCl 2 , 2.5; KH 2 PO 4 , 1.2; and NaHCO ;) , 24.9. This initial perfusate was warmed to 37-38°C and equilibrated with a 95% O 2 -5% CO 2 gas mixture to give a pH of 7.4. Other values of pH were obtained by equilibrating with a gas containing different proportions of O 2 and CO 2 . Samples of freshly prepared stock solutions of adenosine or theophylline (Sigma Chemical Co.) were added to the per...
In the anesthetized dog, blood flow or metabolic rate was varied in kidney, hindlimb, or heart (experimental organ) while simultaneously diverting a portion of the venous outflow through forelimb or kidney (bioassay organ). The resistance to blood flow through the experimental organ gradually rose in the first few minutes following a large increase in flow and gradually fell following a large decrease in flow. Resistance to blood flow through an experimental organ (hindlimb) fell following increase in metabolic rate. In each case, bioassay organ resistance changed in the same direction when the assay organ was the forelimb and in the opposite direction when the assay organ was the kidney. These findings suggest that active hyperemia, reactive hyperemia, and autoregulation of blood flow result, at least in part, from alteration in the chemical environment of the blood vessels. Other findings in this study support the possibility that adenosine triphosphate contributes to the change in environment.
Lymph was collected from a vessel in the hilar region of the kidney in 33 dogs. Care was taken to leave other renal lymphatics undisturbed. Renal lymph and urine were collected continuously and arterial blood periodically. The renal lymph-to-arterial plasma ratios of all endogenous substances measured were essentially unity except urea, total protein, and calcium, whose ratios were less than one. Intravenously infused PAH and inulin appeared in renal lymph in concentrations of 58 and 80%, respectively, of their concentrations in arterial plasma. In five dogs, both hilar and capsular lymph was collected simultaneously. Sodium concentrations were similar in these samples and in neither was sodium more concentrated than in arterial plasma.
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