Abnormal forearm vascular responses in the carcinoid syndrome: the role of kinisns and kinin-generating system.

Mason, Dean T.; Melmon, Kenneth L.

doi:10.1172/jci105475

Cited by 40 publications

(16 citation statements)

References 42 publications

(58 reference statements)

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“…Kinin concentrations in all neonatal blood samples (umbilical and placental) were above normal and were equivalent or greater than those found in patients with carcinoid syndrome during a flush (23,24). Such concentrations of kinin would be sufficient to produce pharmacologic effects (25) and could certainly contribute to a decrease in pulmonary and systemic vascular resistance, as well as to constriction of vessels key to neonatal circulatory adaptation. The source of kinin may be the blood vessels, the fetal organs, or the plasma itself.…”

Section: Resultsmentioning

confidence: 99%

Kinins: Possible Mediators of Neonatal Circulatory Changes in man

Melmon¹,

Cline²,

Hughes³

et al. 1968

J. Clin. Invest.

122

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A B S T R A C T Bradykinin is a potent constrictor of the human umbilical artery and vein and the ductus arteriosus of the lamb in vitro at oxygen tensions above 40 mm Hg (comparable to those in the newborn infant). Bradykinin is also capable of producing remarkable dilatation of the pulmonary vasculature of the lamb. Theoretically, kinins are capable of effecting some of the rapid circulatory changes required of the neonate. The present study was undertaken to investigate the role of kinins as mediators of such changes.The concentration of bradykinin in the cord blood of 56 newborn infants at the time of birth was significantly higher than the blood level in adult subjects (12.8 ± 4.3 ng/ml compared with 2.0 ng/ml or less). Cord arterial blood contained inactive kinin precursor (kininogen) and inactive kinin-releasing enzyme (kallikrein). Plasma kallikrein was activated, with subsequent kinin formation and kininogen depletion, by exposure to neonatal granulocytes or by a decrease in the temperature of cord blood from 37 to 270C. A comparable decrease in the temperature of umbilical arterial blood occurs at the time of birth.Activation of kallikrein by neonatal granulocytes was dependent on cell concentration and required oxygen tensions comparable to those in the neonate but above the range in the fetus. Granulocytes of the neonate, unlike those of adult subjects, lacked kininase activity.

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Section: Resultsmentioning

confidence: 99%

Kinins: Possible Mediators of Neonatal Circulatory Changes in man

Melmon¹,

Cline²,

Hughes³

et al. 1968

J. Clin. Invest.

122

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“…These peptides, the most potent endogenous vasodilators known, can produce significant decreases in peripheral vascular resistance and reflex increases in venous tone (thus contributing to pooling in the affected microcirculation) at concentrations well below those found in the primate during endotoxin infusion (4,5). Despite the brief half-life of circulating kinins (approximately 30 sec) (17), concentrations were elevated for more than 2 hours.…”

Section: Discussionmentioning

confidence: 99%

“…changes characteristic of the early phase of endotoxin shock (5). Therefore, we have investigated: (1) the cardiovascular alterations in unanesthetized rhesus monkeys 1 infused with Escherichia coli or Pseudomonas pseudomaUei endotoxin; 2 (2) kinin production during the shock period; and (3) the source and mechanism of kinin production.…”

Section: Nies Forsyth Williams Melmonmentioning

confidence: 99%

Contribution of Kinins to Endotoxin Shock in Unanesthetized Rhesus Monkeys

Nies

Forsyth

Williams

et al. 1968

Circulation Research

135

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The effects of endotoxin (Escherichia colt and Pseudomonas pseudomallei) were studied in 18 unanesthetized rhesus monkeys restrained in primate chairs. Indwelling arterial and venous catheters were used for hemodynamic measurements and blood sampling. Whole blood kinin, plasma kininogen, lysosomal enzymes, complete blood counts, and blood gas tensions were measured. Within an hour of beginning the infusion of the endotoxin, the mean arterial pressure and systemic peripheral resistance decreased significantly in the 18 experimental monkeys compared to 13 control monkeys. These early changes were associated with significant elevation in whole blood kinin concentration and a decrease in plasma kininogen. All of these early changes were most marked in the animals that died. Granulocytopenia occurred within 15 minutes, and the concentration of free lysosomal enzyme in the plasma rose 2 hours after endotoxin infusion. The pretenninal phase of shock was characterized by a low peripheral vascular resistance and decreasing cardiac output without elevation of kinin levels. These findings support the hypothesis that kinins play a pathogenetic role in the early phase of endotoxin-induced shock and that the severity of the early phase may influence the animal's survival. The relation of kinins to other vasoactive substances released after endotoxin-induced shock is unknown.

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“…ASA = acetylsalicylic acid.DISCUSSIONSpontaneous flushing, sometimes accompanied by hypotension, wheezing and diarrhoea, is probably mediated by the release into the circulation of vasoactive agents acting directly on the vascular smooth muscle or may be mediated by vasomotor nerves (1). Catecholamines(21), kinins(22), serotinin(7), histamine (23), prostaglandins (24), endogenous opioids (25), substance P(26), VIP (lo), and somatostatin(12) have been suggested as possible aetiologic agents in the pathogenesis of flushing reactions seen in patients with flushing due to chloropropamide-alcohol(24)(25)(26), menopause(1,27), carcinoid (1,7) and the other neoplasia (1). Medical management, which includes the administration of clonidine(28,29), indomethacin(30), aspirin (31), naloxone (32), cyproheptadine (33), cimetidine (34), and steroids(35), has been tried with variable success.…”

mentioning

confidence: 99%