Atrial natriuretic factor increases vascular permeability.

An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

Vascular relaxation and cGMP in hypertension.

Isolated aortas from hypertensive rats have a decreased relaxation response to acetylcholine chloride (ACh), the calcium ionophore A23187, and sodium nitroprusside (SNP). Since the vascular relaxation responses to these vasodilators may be a result of increases in guanosine 3',5'-cyclic monophosphate (cGMP), we measured the cGMP response to these agents in isolated aortas from normotensive rats and rats with either mineralocorticoid-induced hypertension (DOCA), renovascular hypertension (1K1C), or coarctation-induced hypertension (Coarc). The aortas from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to ACh and A23187. Rises in cGMP in response to SNP were also attenuated in aortas from the hypertensive rats, even at concentrations that induced maximum relaxation of blood vessels from normotensive and hypertensive rats. The relaxation responses to atrial natriuretic factor (ANF) and the cGMP generated in isolated aortas by ANF were attenuated in hypertension. Removal of the endothelium markedly attenuated cGMP generation in response to ANF in vessels from normotensive and Coarc rats, but the relaxation responses to ANF were unaltered in vessels after the removal of the endothelium. The reversal of experimentally induced hypertension was associated with increases in cGMP levels following exposure of the isolated vessels to ACh. Also, vessels treated with methylene blue relaxed in response to SNP despite inhibition of cGMP accumulation. The decreased relaxation response to endothelium-dependent vasodilators is accompanied by decreases in cGMP accumulation; the decreased vascular cGMP content in response to endothelium-dependent vasodilators is not due to increases in phosphodiesterase activity of vascular smooth muscle; and SNP may relax blood vessels through "cGMP-dependent" and "cGMP-independent" mechanisms.

Effect of iron and liver injury on the pathogenesis of Vibrio vulnificus.

Noncholera vibrio species can cause necrotizing soft tissue infections and cellulitis in addition to gastroenteritis. Cellulitis and necrotizing soft tissue infections frequently occur in people with liver disease or in people who are in some way a compromised host. We studied the effect of Vibrio vulnificus on the mortality of mice treated with carbon tetrachloride, an agent that causes liver damage, Desferal, an iron-chelating agent, or iron. The LD50 of V. vulnificus is approximately 2.5 X 10(6) CFU. In mice, desferal lowered the LD50 to less than 100 CFU, and carbon tetrachloride lowered the LD50 to approximately 1000 CFU. Twenty percent of the mice that survived had necrosis of the skin overlying the injection site. These studies demonstrate that liver damage and iron chelating agents increase mortality and necrotizing soft tissue infections caused by V. vulnificus.

Phorbol ester, vascular relaxation, and cyclic guanosine 3',5'-monophosphate.

The relaxation of phenylephrine-contracted blood vessels by acetylcholine, nitroprusside, or atrial natriuretic factor has been linked to elevations in cyclic guanosine 3',5'-monophosphate (cGMP). Also, 8-bromo-cGMP can induce vascular relaxation in isolated vascular smooth muscle contracted with phenylephrine. We determined whether these cGMP-dependent vasodilators could relax isolated rat aortas contracted with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. cGMP was measured by radioimmunoassay. Acetylcholine, nitroprusside, and atrial natriuretic factor induced relaxation in vascular smooth muscle contracted by 12-O-tetradecanoylphorbol-13-acetate. These relaxation responses were accompanied by elevations of cGMP. However, the sensitivity to these vasodilators was markedly decreased in phorbol ester-contracted vessels compared to phenylephrine-contracted vessels. Nifedipine and superoxide dismutase induced small but significant relaxations in phorbol ester-contracted vessels; however, blood vessels contracted with phenylephrine and phorbol ester relaxed completely with papaverine. There was a marked decrease in sensitivity to 8-bromo-cGMP in phorbol ester-treated vessels compared to phenylephrine-contracted vessels. Contractions induced by phorbol ester were not inhibited by amiloride or chlorpromazine. Also, following incubation in potassium-free salt solution, vessels incubated with phenylephrine or phenylephrine and phorbol ester underwent similar relaxations when exposed to potassium chloride. The contractile state induced by phorbol ester has decreased sensitivity to cGMP-dependent vasodilators. This may be due to nonspecific effects of the phorbol ester or to the mechanism by which protein kinase C activation maintains vascular tone.

Necrotizing soft-tissue infections caused by marine vibrios.

Halophilic, noncholera marine Vibrio bacteria can cause septicemia, gastroenteritis, cellulitis, and necrotizing fasciitis. We describe six patients with necrotizing fasciitis and review 12 cases described previously. The 18 patients included 14 men and four women. Their ages ranged from 32 to 79 years (average 58.1 years). Eleven patients were older than 55 years. Nine infections were caused by V. vulnificus, three by V. parahaemolyticus, and one by V. alginolyticus. In five cases the Vibrio species was not identified. Twelve patients had associated conditions that might have made them more susceptible to these infections, such as cirrhosis, steroid therapy, hemochromatosis, and multiple myeloma. These infections usually occur in apparently insignificant wounds (puncture wounds, insect bites) exposed to sea water or fish. Treatment is by debridement and antibiotic therapy. Three patients required amputation to control the infection. Six (33.3%) of the 18 patients died.