Humoral agent from calf lung producing pulmonary arterial vasoconstriction.

Saline washings obtained in vivo from the lung of young calves produce pulmonary hypertension upon intrayascular (systemic or pulmonary) injection into either the dog or the calf. This pulmonary hypertension is produced by vasoconstriction of small, precapillary pulmonary vessels. The active agent, pulmonary arterial constrictor substance, differs chemically and physiologically from other substances which have been investigated with respect to vasomotor activity in the pulmonary circulation. Although the chemical nature of the active agent is not known it appears to have a relatively large molecular weight. Whether this agent plays a role in the physiological regulation of the pulmonary circulation is not known.

Dissociation of bradycardia and arterial constriction during diving in the seal Phoca vitulina.

Bradycardia associated with diving in the harbor seal has been dissociated from the arterial constrictor response by intracardiac pacing. Development of arterial constriction does not depend upon the development of bradycardia. During pacing, arterial constriction continues in the absence of bradycardia. Increases in heart rate to values greater than 120 beats per minute during a dive produce a progressive decrease in mean aortic pressure, which suggests that one major function of bradycardia is to reduce cardiac output, thus matching left ventricular output to the restricted vascular bed and decreased venous return associated with diving.

Arterial constrictor response in a diving mammal.

Angiograms were obtained in the harbor seal, Phoca vitulina, in air and during diving. During diving there is arterial constriction of the vascular beds of muscle, skin, kidney, liver, spleen, and presumably of all vascular beds except those perfusing the brain and heart. There is sudden constriction and narrowing of muscular arteries close to their origin from the aorta. Constriction of small arterial branches is so intense that blood flow is essentially lost in all involved organs.

Pathogenic role of cyclic AMP in the impairment of urinary concentrating ability in acute hypercalcemia.

A possible association between the impairment of urinary concentrating ability and an impairment of the vasopressin-dependent cyclic AMP system in hypercalcemia was investigated in rat kidneys both in vivo and in vitro. The increases of urinary osmolality and negative free water clearance and the increase of urinary cyclic AMP excretion by vasopressin injection were significantly less in the hypercalcemic rats than in the control rats. The increase of cyclic AMP concentration by vasopressin in renal medullary tissue was significantly less in the slices obtained from the hypercalcem'c rats than in those obtained from the control rats. The activation of adenylate cyclase by vasopressin was significantly less in the group with an increased concentration of calcium in media than the control group, but phosphodiesterase activity was not affected by calcium concentration in the media. These data suggest that the impaired urinary concentrating ability in hypercalcemic kidneys is due at least in part to the direct inhibitory effect of calcium on the vasopressin-dependent cyclic AMP system at the level of adenylate cyclase in renal medulla.

Effects of catecholamines and their interaction with other hormones on cyclic 3',5'-adenosine monophosphate of the kidney.

Catecholamines have several physiological effects on the kidney. These include: (a) stimulation of renin synthesis in the cortex: (b) antidiuresis by beta adrenergic agents; and (c) diuresis by alpha adrenergic stimulation. The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the renal actions of catecholamines was evaluated by measuring the effects of several adrenergic agents on cyclic AMP concentration in the dog kidney. Beta adrenergic activity increased cyclic AMP concentration in the renal cortex, a finding consistent with the hypothesis that beta-adrenergic stimulation augments renin synthesis by increasing cyclic AMP generation. Beta adrenergic stimulation, like vasopressin, increased cyclic AMP concentration in the renal medulla. This suggests that beta adrenergic stimulation causes antidiuresis by augmenting cyclic AMP generation in the renal medulla. Alpha adrenergic activity inhibited the effect of vasopressin to stimulate cyclic AMP generation. These results support the hypothesis that the diuretic effect of alpha adrenergic stimulation is mediated by inhibition of the effect of vasopressin to increase cyclic AMP generation.

The determination of total body exchangeable O2 stores.

A method is described for the measurement of total body exchangeable oxygen stores (TBO(2)). It is based on the dilution of the stable oxygen isotope, (18)O(2), by the body exchangeable oxygen stores under circumstances in which (18)O(2) steady-state equilibrium was evaluated simultaneously for both arterial and venous blood compartments. After evaluation of several simplifying assumptions, TBO(2) values in dog, normal man, and anemic patients were measured. The magnitude of the exchangeable nonlung oxygen stores was 11.0 +/- 3.1 ml/kg (SD) in 5 dogs, 11.9 +/- 2.1 ml/kg in 10 normal subjects, and 7.0 +/- 1.6 ml/kg in 8 patients with severe anemia (hematocrits of 25% or less).

Hypomagnesemia following the diuresis of post-renal obstruction and renal transplant.

Three unusual cases are described which demonstrated hypomagnesemia and symptoms resembling magnesium deficiency syndrome. The hypomagnesemia was most likely secondary to urinary losses from diuresis following release of post-renal obstruction and renal homotransplantation. Heretofore, this association has not been described. Case 1 was unique because of the post-obstructive diuresis in the face of marked renal impairment. Case 2 is noteworthy because of the profound hypomagnesemia, 0.4 mEq/1, and because of the development of congestive heart failure. The rapid improvement noted in cardiac function with magnesium replacement suggests a relationship to magnesium deficiency.

Pardaxin increases solute permeability of gills and rectal gland in the dogfish shark (Squalus acanthias).

The action of the ichthyotoxic secretion of the Red Sea flatfish Pardachirus marmoratus and its derived toxin, pardaxin, was examined in the dogfish shark (Squalus acanthias). Pardaxin was more toxic when administered to the bathing medium than when injected into a dorsal artery and it transiently diminished the spiracular rate and caused a severe struggling response in the adult shark only when administered to the head region of the shark. Pardaxin caused a transient leakage to urea and sodium between the shark and the seawater. In the isolated perfused rectal gland pardaxin irreversibly reduced the rate of chloride secretion and concentration gradient of urea between perfusate and rectal gland fluid. In addition, ultrastructural studies on the rectal gland showed that ionic lanthanum penetrated the tight junctions and foci of cell necrosis were observed. These studies indicate that in shark the gills are the most probable target of the toxicity of pardaxin.

Effects of hemodialysis and saline loading on body fluid compartments, plasma renin activity and blood pressure in patients on chronic hemodialysis.

The influence of one hemodialysis session and of subsequent loading by 1.5-2 liters N saline on blood pressure, PRA and body fluid compartments was assessed in seven patients with chronic renal failure on maintenance hemodialysis. Dialysis caused only slight decreases in plasma volume, ECV and in TEBS. Lying mean blood pressure by 5-10 mm Hg and PRA increased by 30%. Saline loading resulted in a significant increase in plasma volume by 0.4 liters and in blood pressure by 10-5 mm Hg, but in a decrease in PRA by 40%. The changes in mean blood pressure correlated positively with the changes in plasma volume, and negatively with the changes in PRA. It is concluded that the renin-angiotensin system in patients on chronic hemodialysis still functions as one of the adjustment mechanisms for the circulatory homeostasis, when challenged by volume loss or volume and sodium loading.

Structure of tight junctions during Cl secretion in the perfused rectal gland of the dogfish shark.

In epithelia that secrete sodium chloride, high-conductance tight junctions between cells have been proposed as the primary pathway for transepithelial sodium flux. We examined the properties of tight junctions in the perfused rectal gland of the dogfish shark during basal secretion and following adenosine 3',5'-cyclic monophosphate stimulation of sodium chloride secretion. Freeze-fracture electron microscopy revealed extensive interdigitation of adjacent cells with an associated amplification in the length of tight junctions per area of luminal surface, averaging 102 +/- 4.7 m/cm2 in outer regions of 80 +/- 6.7 in inner regions of the gland. Marked heterogeneity of junctional structure was present with junctional elements varying from single strands to three duplex elements and junctional depth varying from 15 to 60 nm. In glands perfused with lanthanum chloride, ionic lanthanum filled the intercellular space up to but not through the tight junctions. Characteristics of tight junctions were not different during basal and maximally stimulated sodium chloride secretion. These studies define tight junctions in the rectal gland as an anatomical barrier capable of restricting the passage of relatively small molecules such as urea while providing a greatly amplified junctional area for the passive diffusion of sodium and water.