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We have reported that low doses of endothelin-3 (ET-3) elicited continuous vasodilation of rat mesenteric arteries, which is possibly related to endothelium-derived relaxing factor (EDRF). In order to clarify whether or not the vasodilating effects of ET-3 are associated with EDRF, we examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced vasodilation of rat mesente-Hc arteries. Infusion of 50 microM L-NMMA inhibited the vasodilation induced by 10(-13) M ET-3 and rather elicited an increase in perfusion pressure, which itself was decreased by infusion of 150 microM L-arginine. In the presence of 50 microM L-NMMA, 10(-13) M ET-3 did not elicit any vasodilation of the mesenteric arteries preconstricted with NE, in which 150 microM L-arginine, but not D-arginine, caused considerable vasodilation. These data suggest that the vasodilating effects of low doses of ET-3 are associated with EDRF as an endothelium-derived nitric oxide.

Spironolactone was administered to spontaneously hypertensive rats (SHRs) in order to examine the urinary excretions of prostaglandin E2 (PGE2) and kinin. Thirteen SHRs were divided into 2 groups: 0.1 ml of sesame oil was administered to one group (the spironolactone-lactone-untreated group, n = 6) and 20 mg of spironolactone in 0.1 ml of sesame oil was administered to the other group (the spironolactone-treated group, n = 7) by the subcutaneous route for 10 days in succession. Determinations were then made of the body weight, blood pressure, urine volume, and excretion levels of Na, K, kinin and PGE2 in the 24-hour urine. After the animals had been killed by decapitation, blood samples were drawn for determination of the plasma renin activity (PRA). The results obtained indicated decreased blood pressure and increased urinary Na excretion in the spironolactone-treated group. On the other hand, the PGE2 excretion level in the 24-hour urine decreased markedly immediately after administration of spironolactone (p

The locus coeruleus was subjected to biphasic electrical stimulation, and a group of deoxycorticosterone acetate (DOCA)-salt hypertensive rats revealed a greater pressor response than a group of normotensive control rats. The pressor threshold current (i.e. minimum current to raise the arterial pressure by 10 mm Hg) of DOCA-salt hypertensive rats was also lower. The threshold current was low even in the prehypertensive stage of DOCA-salt treated rats. During arterial pressure fall, the pressurethreshold current lowered only in normotensive rats and neither group underwent a change during pressure rise. These data indicated that the locus coeruleus had a pressor role and it had been accelerated in DOCA-salt treated rats before hypertension was evident. Following bilateral electrical lesions of the locus coeruleus no significant differences were observed in the arterial pressure changes, while vascular reactivity to norepinephrine did not differ between the two groups. The results suggest that the locus coeruleus may be involved in the development of hypertension but may not be important in the maintenance of it.

The effects of elastase on blood pressure (B.P.) and the urinary excretions of prostaglandins (PGs) and catecholamines in the spontaneously hypertensive rat (SHR) were investigated. Male SHRs (n = 20), castrated at 4 weeks of age, were divided into 2 groups. Elastase was then dissolved in saline (5 mg/ml) and injected subcutaneously (10 mg/kg of body weight) into the SHRs of one of the 2 groups (n = 10) at 5 to 13 weeks of age, and the same dose of saline only was injected subcutaneously into the SHRs of the other group (n = 10) as a control during the same period. B.P. was measured by the tail-cuff method every 2 weeks. Urine sampling and measurement of body weight (B.Wt.) were also performed every 2 weeks. The B.P. in the elastase-administered group (184.1 ± 3.3 mmHg) was found to be significantly lower (p < 0.02) than that of the control group (198.0 ± 4.3) at 9 weeks of age. A significant difference (p < 0.01) in B.P. between the control group (204.0 ± 4.5) and the elastase-administered group (187.3 ± 2.7) was also observed at 13 weeks of age. The urinary excretion of 6-keto-prostaglandin F1α (6-keto-PGF1α) in the control group (5.1 ± 0.4 ng/day/100 g B.Wt.) at 11 weeks of age was significantly lower (p < 0.05) than that of the elastase-administered group (10.4 ± 1.3). The urinary excretions of norepinephrine (NE) and epinephrine (E) in the control group (345.1 ± 39.4 ng/day/100 g B.Wt. (NE), 54.8 ± 8.8 ng/day/100 g B.Wt. (E)) were found to be significantly higher (p < 0.02) than those in the elastase-administered group (216.3 ± 27.7 (NE), and 23.0 ± 3.1 (E)) at 13 weeks of age. The present experiments demonstrated a retardation in the development of hypertension, an increment in the urinary excretion of 6-keto-PGF1α and a decrement in the urinary excretion of catecholamines in the elastase-administered group as compared to the control group. These findings suggest that elastase causes retardation of the development of hypertension in SHRs by some unknown mechanism that increases the excretion of 6-keto-PGF1α and suppresses the excretion of catecholamines.

Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.

Recently many studies have been done to identify complement pathway activation in renal tissue from patients with renal disease. We examined whether tissues obtained by renal biopsy from such patients would fix guinea pig complement. Nine out of 15 patients with systemic lupus erythematosus (SLE), 4 out of 7 patients with mesangiocapillary glomerulonephritis (MCGN), and 2 out of 7 cases with acute glomerulonephritis (AGN) fixed guinea pig C3. We found that tissues from 5 out of 9 guinea pig C3-positive SLE cases fixed guinea pig C4, while none of the guinea pig C3-positive tissues from patients with MCGN or AGN fixed guinea pig C4. These guinea pig C3-positive renal tissues were further studied for interaction with C4-deficient guinea pig serum, EDTA guinea pig serum, heated guinea pig serum, and EGTA Mg2+ guinea pig serum. The results indicated that activation of both the alternate and classical complement pathways occurred with tissues from patients with SLE, while activation of the alternate pathway occurred with MCGN and AGN. Results for tissues from AGN and MCGN patients indicated the presence of C3 convertase and protease which interacted with guinea pig C3.