Strong, Cameron G.

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous inject ons (3 mg day—1 kg—1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), and ten rabbits with one-kidney Goldblatt hypertension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1·15 to 0·2 ng/ml, sem 0·2; P < 0·01) and plasma renin activity (20 to 3 ng h—1 ml—1, sem 1, P < 0·01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31·5 ng h—1 ml—1, sem 3 and 4 respectively; P < 0·01) and plasma prostaglandin E2 (1·2 to 3·4 ng/ml, sem 0·2 and 0·4 respectively; P < 0·05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7·6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, sem 7·7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, sem 4 and 6 respectively; P < 0·01) and decreased renal function (plasma creatinine 0·9 ± 0·04 to 3·5 ± 1 mg/100 ml, sem 0·04 and 1 respectively; P < 0·01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.

1. Hepatic metabolism of renin activity was studied in seven normal dogs, twelve dogs with acute hepatic allograft rejection, five dogs with chronic toxic hepatitis and in seven isolated canine liver preparations. 2. Renin activity was measured by radioimmunoassay in hepatic arterial, portal venous, and hepatic venous plasma (PRA), in bile (BRA) and in perfusate (PsRA). 3. There was a significant gradient of PRA across the normal liver (P < 0.03) and of PsRA across the isolated liver (P < 0.05). 4. There was no significant PRA gradient across the liver of dogs with allograft rejection (acute hepatic necrosis). 5. Dogs with chronic toxic hepatitis showed decreased fractional extraction of PRA but otherwise their data were normal. 6. There was a significant difference between portal venous PRA (8.69 ±1.51 ng ml−1h−1) and hepatic arterial PRA (5.67±1.91 ng ml−1h−1) (P < 0.05). 7. BRA accounted for only 0.04% of hepatic extraction of PRA, suggesting that more important mechanisms for hepatic renin metabolism are binding or destruction of renin by the hepatic tissue.

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K + , and decreased bath concentration of Na + . The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.