SUMMARY To investigate the role of circulating humoral substances in the patbogenesis of increased vascular wall water and sodium concentration in experimental hypertension, rabbit aortic media explants were cultured in tissue culture medium supplemented (10-20%) with serum obtained from the same dogs (n = 7): \) before the induction of hypertension; 2) after wrapping one kidney in silk (two-kidney perinephritic hypertension, 2-KPHT); and 3) after contralateral nephrectomy (1-KPHT). Cultures also were run with serum of sham-wrapped and then unilaterally nephrectomized nonnotenshe dogs (n = 4). After 3 weeks of culture, the explants were harvested, and their water, sodium and potassium concentration was measured. Compared to the composition of explants cultured in prehypertensive serum, the water concentration of explants cultured in 1-KPHT and the sodium concentration of explants cultured in 2-KPHT and 1-KPHT serum were increased concentration in experimental and human hypertension has been known for many years 1 and has been generally ascribed to the effects of increased intraluminal pressure.2 Recent reports of similar changes in the veins of experimental animals with hypertension raised the possibility that humoral or neural stimuli may also play a role in the pathogenesis of abnormal vascular wall composition in hypertension.8 ' * Evidence for the role of humoral factors was found in parabiotic rats, one of which was made hypertensive by partial constriction of one renal artery.6 There were similar increases in the water and electrolyte content of the vena cavae of hypertensive rats and their normotensive parabiotic mates. From these experiments it could not be determined whether the unknown humoral factor, originating from the hypertensive rat, affected venous wall metabolism directly or whether its action was mediated through other mechanisms. The purpose of the present experiments was to investigate the direct effect of serum from hypertensive dogs on the water and electrolyte composition of rabbit aortic media in culture.
Methods
Preparation of DogsMale mongrel dogs weighing 18-27 kg were trained to lie quietly during percutaneous femoral artery puncture for blood pressure measurements. A resting mean arterial pressure of less than 130 mm Hg was documented in each dog on at least one occasion. In seven dogs anesthetized with pentobarbital (30 mg/kg I.V.), one kidney was wrapped in silk to induce perinephritic hypertension. Two weeks later, the contralateral kidney was removed surgically. Four dogs underwent sham-wrapping of one kidney and then contralateral nephrectomy 2 weeks later. The operations were performed as described in a previous publication.6 Antibiotics were not used either pre-or postoperatively. Blood pressure measurements were repeated before nephrectomy and again 4 weeks after nephrectomy. During the entire study period the dogs were maintained on a diet of standard dog chow and water ad libitum.