Increased prostaglandin synthesis in the unclipped kidney of one-kidney, one clip hypertensive rats.

Reversal of one-kidney, one clip (1-K, 1C) hypertension by removal of the renal artery clip is accompanied by increased renal and vascular prostaglandin (PG) production. It was postulated that PG biosynthesis is stimulated in the unclipped hypertensive kidney. In order to test this hypothesis, we compared urinary excretion of PGE2 and 6-keto-PGF1 alpha (a breakdown product of PGI2) in perfused kidneys isolated from 1-K, 1C hypertensive rats, 1-K, sham-clipped rats and 1-K, 1C rats which had failed to become hypertensive. Urine was collected over 15 min periods at perfusion pressures of 100, 150 and 200 mmHg. At perfusion pressures of 100 and 150 mmHg there was no significant difference in PGE2 excretion between the three groups. In contrast, 6-keto-PGF1 alpha excretion at 150 mmHg was higher in the hypertensive rats compared with the sham-clipped (P less than 0.05) and failed hypertensive (P less than 0.01) rats. At 200 mmHg, both PGE2 and 6-keto-PGF1 alpha were significantly higher in the hypertensive rats than in the control groups. These increases in PG excretion were clearly dissociated from changes in urinary flow rates. The findings support the hypothesis of increased synthesis of renal vasodilatory and natriuretic PGs in 1-K, 1C hypertension which is particularly evident at higher perfusion pressures, such as may be encountered when the hypertensive kidney is unclipped and exposed to high arterial pressure.

Dexamethasone attenuates reversal of hypertension in one-kidney, one-clip rats.

This study examines the effect of dexamethasone (Dex), a phospholipase A2 inhibitor, on the reversal of 1-kidney, 1-clip (1K,1C) hypertension and the synthesis of phospholipase A2-dependent products. Male Sprague-Dawley 1K,1C hypertensive rats [blood pressure (BP) greater than 190 mmHg] were allocated to three groups: two groups were given daily oral doses of Dex (0.142 mg/kg in water) for 72 h, whereas the third group was given water only (controls). One of the Dex-treated groups was then sham unclipped (n = 9), while the other Dex-treated group (n = 8) and the control group (n = 8) were unclipped. Dex attenuated the BP fall in the unclipped (223 +/- 8-148 +/- 9 mmHg) compared with the control unclipped (226 +/- 9-114 +/- 5 mmHg) animals (P less than 0.005). Aortic 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) was reduced in unclipped Dex-treated rats (13.4 +/- 1.2 ng/mg) compared with unclipped control rats (16.3 +/- 1.4 ng/mg; P less than 0.05) but was higher than in the sham-unclipped Dex group (11.5 +/- 1.2 ng/mg; P less than 0.05). Serum thromboxane B2 (TxB2) in the unclipped Dex-treated group was lower than in the unclipped control rats (P less than 0.05) but higher than in sham-unclipped rats (P less than 0.05). Dex significantly increased urinary prostaglandin E2 (PGE2) excretion, whereas urinary 6-keto-PGF1 alpha was unaltered. After unclipping, both urinary PGE2 and 6-keto-PGF1 alpha increased significantly, although there was no obvious difference between Dex-treated and control animals. These findings demonstrate opposite effects of Dex on renal compared with extrarenal prostanoid synthesis and support the hypothesis that attenuation of aortic 6-keto-PGF1 alpha synthesis may be responsible for the smaller fall in BP after unclipping in Dex-treated rats.

Increased levels of platelet-activating factor (1-O-alkyl-2-acetylglycerophosphocholine) in blood after reversal of renal clip hypertension in the rat.

1. This study analyses whole blood in acutely unclipped one-kidney, one-clip (1K, 1C) hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the rapid blood pressure (BP) fall seen after unclipping. 2. Hypertensive 1K, 1C rats were anaesthetized and a carotid and jugular cannula were inserted for BP measurement and anaesthetic infusion respectively. After a stable level of anaesthesia was attained, the constrictive clip was removed and BP was recorded for 30 min. 3. Blood was drawn from the aorta directly into ice-cold acetone. The extract was analysed for PAF by a bioassay using 5-hydroxy-[14C]tryptamine-labelled platelets. 4. Rats which showed a BP fall had elevated levels of PAF [55 +/- 6 (SEM) pg/ml] (P less than 0.01). 5. This supports the hypothesis that activation of PAF biosynthesis may be a mechanism contributing to the fall in BP seen after unclipping the 1K, 1C hypertensive rat.

Increased aortic PGI2 and plasma lyso-PAF in the unclipped one-kidney hypertensive rat.

Previous studies have implicated vasodilatory prostaglandins (PGs) in the reversal of hypertension following unclipping in the one-kidney, one-clip (1K,1C) hypertensive rat. The capacity of the aorta to synthesize prostacyclin (PGI2) was compared in clipped (group A, n = 9), unclipped (group B, n = 8 and group D, n = 9), and sham-unclipped (group C, n = 9) 1K,1C hypertensive rats. The involvement of platelet-activating factor (PAF), a potent renal antihypertensive phospholipid, in the reversal of renal clip hypertension was also examined. Hypertensive rats [systolic blood pressure (BP) greater than 180 mmHg] were fed a synthetic diet for 4 wk, after which group A was killed immediately, group C was sham-unclipped, and groups B and D unclipped and killed 24 h later. Blood was drawn for the measurement of plasma lyso-PAF (the precursor of PAF) and the aorta removed for determination of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of PGI2). BP fell substantially in the unclipped rats (groups B and D) but did not change in the sham-unclipped rats (group C). Mean aortic 6-keto-PGF1 alpha was increased in the unclipped groups [group B, 15.4 +/- 2.4 (SE) ng/mg; group D, 10.8 +/- 2 ng/mg] compared with group A (7.7 +/- 1 ng/mg) and group C (7.1 +/- 1 ng/mg) (H = 13.74, P less than 0.01). Plasma lyso-PAF was also significantly increased in the unclipped (group D, 261 +/- 26 ng/ml) vs. the sham-unclipped group (group C, 211 +/- 23 ng/ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in prostanoid synthesis in response to diet and hypertension in one-kidney, one clip rats.

This study was designed to examine the effects of diets that alter prostaglandin biosynthesis on the blood pressure in one-kidney, one clip rats with established hypertension and to compare the prostanoid generating capacity of hypertensive animals with those that remained normotensive. Rats attaining blood pressures of at least 180 mm Hg within 8 weeks of nephrectomy and renal artery stenosis were paired by weight and blood pressure and then placed on either a safflower oil or a prostaglandin I2 inhibitory diet (cod liver oil-linseed oil mix) for 4 weeks. Animals with blood pressures of less than 150 mm Hg were also paired for the same two dietary regimens. Comparison between the two blood pressure groups revealed that on both dietary regimens hypertensive rats produced significantly more aortic 6-keto-prostaglandin F1 alpha and serum thromboxane B2. Rats on the cod liver oil-linseed oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid and significantly impaired ability to generate serum thromboxane B2 (36%), aortic 6-keto-prostaglandin F1 alpha (65%), renal homogenate 6-keto-prostaglandin F1 alpha (64%) and prostaglandin E2 (58%), and urinary prostaglandin E2 (70%) and 6-keto-prostaglandin F1 alpha (52%). Despite these differences in prostanoid synthesizing capacity, no differences in blood pressure were observed between the safflower oil-fed rats and rats fed cod liver oil-linseed oil within either the hypertensive or normotensive groups. These results suggest that prostanoids do not play a major role in maintaining blood pressure in established one-kidney, one clip hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dietary alteration of prostaglandin synthesis on blood pressure and the reversal of hypertension in the one-kidney, one-clip rat.

This study examined the effect of diet-induced changes in prostaglandin synthesis on systolic blood pressure in one-kidney, one clip (1k, 1C) hypertensive rats and on the fall in blood pressure after unclipping. It tested the hypothesis that inhibition of prostaglandin synthesis exacerbates hypertension in this model and prevents complete reversal after unclipping. Rats with sustained hypertension within 8 weeks of renal artery clipping were fed synthetic diets supplemented to 20% of total energy with either safflower oil (linoleic acid) or a mixture of cod liver oil (90%) (containing eicosapentaenoic acid) and linseed oil (10%) (containing linolenic acid) for 4 weeks. The latter oil mixture resulted in a predictable reduction in kidney PGE2 and 6-keto PGF1 alpha (hydrolysis product of PGI2), aortic 6-keto PGF1 alpha and serum TXB2. However, at the end of 4 weeks dietary treatment there were no differences in systolic blood pressure between the two diet groups, and the blood pressure fall 24 hours after unclipping was similar. These findings therefore do not support a role for prostanoids in the maintenance or reversal of 1K, 1C hypertension.