Kinins: Possible Mediators of Neonatal Circulatory Changes in man

A B S T R A C T To investigate mechanisms of pulmonary edema in respiratory failure, we studied unanesthetized sheep with vascular catheters, pleural balloons, and chronic lung lymph fistulas. Animals breathed either a hypercapnic-enriched oxygen (n = 5) or a hypercapnic-hypoxic (n = 5) gas mixture for 2 h. Every 15 min blood gases, pressures, cardiac output, lymph flow (Qlym), plasma and lymph albumin (mol wt, 70,000), IgG (mol wt, 150,000), IgM (mol wt, 900,000), and blood bradykinin concentrations were determined. In both groups, cardiac output and pulmonary arterial pressures increased, whereas left atrial pressures were unchanged. Acidosis alone (arterial pH = 7.16, Paco2 = 81 mm Hg, Pao2 = 250 mm Hg) resulted in a doubling of lymph flow, a small increase in protein flux, and a decrease in lymph to plasma protein concentration (L/P) ratio for all three proteins. Acidotic-hypoxic animals (arterial pH = 7.16, Paco2 = 84 mm Hg, Pao2 = 48 mm Hg) tripled Qlym. In these animals the increase in lymphatic flux of albumin, IgG, and IgM was significantly (P < 0.05) greater than that seen in either the acidosis alone group or in animals where left atrial pressures were elevated (n = 5; P < 0.05). Also, their percent increase in flux of the large protein (IgM) was greater than for the small protein (albumin) (P < 0.05). With acidosis alone, only pulmonary arterial bradykinin concentration increased (1.27+0.25 ng/ml SE), whereas acidosis plus hypoxia elevated both pulmonary arterial bradykinin

Section: Resultsmentioning

confidence: 99%

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

O’Brodovich¹,

Stalcup²,

Pang³

et al. 1981

“…An alternative explanation is that central vasopressin release may be inhibited in renally denervated lambs through loss of renal afferent input, because, at least in the adult, neurosecretion of vasopressin is increased by afferent renal nerve stimulation (39,40). Although there is presently no evidence that afferent renal nerve activity is increased at birth, circulating bradykinin, a substance known to stimulate afferent renal nerves (41), is elevated in the immediate postnatal period (32,33,42). In the present study, however, neither plasma vasopressin nor bradykinin levels were measured.…”

Section: Discussionmentioning

confidence: 99%

Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life.

Smith

Smith²,

Guillery³

et al. 1991

To determine the role of renal sympathetic nerves in influencing renal function during the transition from fetal to newborn life, studies were carried out in conscious, chronically instrumented fetal sheep with either bilateral renal denervation (n = 11) or intact renal nerves (n = 12), 3-6 d after surgery. Endocrine, renal, and cardiovascular parameters were measured before and after delivery of lambs by cesarean section. Blood pressure and heart rate were similar in intact and denervated fetuses, and increased after delivery in both groups. There was also a transient diuresis and natriuresis, in the immediate postnatal period, the response being significantly greater in denervated than intact lambs (P < 0.05). By 24 h postnatally, fluid and electrolyte excretions were similar in both groups, and significantly less than fetal levels. In the absence of renal nerves, the normal rise in plasma renin activity at birth was attenuated. These data provide evidence that renal sympathetic nerves play an important role during the transition from fetal to newborn life, and support the premise that birth is associated with sympathetic activation. (J.

“…Certain cells in the carotid bodies also sense changes in oxygen tension, and produce alterations in adjacent cells sufficient to initiate propagation of afferent nerve impulses to the central nervous system (28). Also, fetal leukocytes in the lung respond to an increase in oxygen tension by stimulating kallikrein activation (29), an important early step in the adaptation of the fetal circulation to extrauterine life. The …”

Section: Discussionmentioning

confidence: 99%

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Stalcup¹,

Lipset²,

Woan³

et al. 1979

A B S T R A C T Endothelial cells in tissue culturedegrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (<2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of Po2 (r = 0.93, P < 0.001), and there was no enzyme activity below a Po2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.