6-ketoprostaglandin-f1-alpha and Hypertension--Renovascular

The effects of specific types of dietary fats on prostanoid biosynthesis, platelet function and the cardiovascular system are reviewed. Studies examining the influence of dietary modification of prostanoid synthesis on blood pressure regulation in normotensive and Goldblatt hypertensive rats showed that while dietary supplementation with either sunflower or linseed oil at 40% of energy respectively stimulated and inhibited tissue prostanoids in vitro and urinary PGE2 excretion in vivo, the development of 1 kidney, 1 clip hypertension was not altered in parallel. Rats on both oil rich diets did however, show an average lower blood pressure than animals on a standard diet. In order to minimise possible non-specific effects of large amounts of dietary fats, the effects on prostanoid metabolism of different oils at 5, 20 and 40% of energy in the diet were studied. While as little as 5% dietary supplements alter fatty acid and prostanoid synthesis in platelets, it appears that higher levels (at least 20%) are required to alter significantly renal prostaglandin metabolism.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Platelets; Cod Liver Oil; Dietary Fats; Dinoprostone; Fatty Acids, Essential; Hypertension, Renovascular; Kidney; Linseed Oil; Prostaglandins; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Safflower Oil; Thromboxane B2

To define the role of the renal nerves of the contralateral kidney in the maintenance of two-kidney, one-clip (2K-1C) renovascular hypertension in rats.. The contralateral kidney of 2K-1C rats was denervated 6 months after induction of hypertension and 4 weeks after nephrectomy of the clipped kidney. Blood pressure, sodium and potassium balance and eicosanoid excretion were measured.. Denervation of the contralateral kidney induced normalization of blood pressure in post-Goldblatt hypertensive rats. This effect was not mediated by a negative sodium balance. Excretion of prostaglandin E2 and thromboxane B2 increased after denervation of the contralateral kidney in both post-Goldblatt hypertensive and post-Goldblatt normotensive rats, while urine extraction remained unaffected.. Afferences from the contralateral kidney appear to participate in the maintenance of 2K-1C renovascular hypertension due to the activation of central mechanisms regulating blood pressure.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Denervation; Dinoprostone; Eicosanoids; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Sprague-Dawley; Sodium; Thromboxane B2; Time Factors

Xueling(p.o.) obviously reduces the aldosterone content of renal hypertension rats, but not affecting markedly the endothelin, atrial natriuretic factor, calcitonin gene-related peptide, thromboxane B2 and 6-keto-prostaglandin F1 alpha. The content reduction of aldosterone is one of the mechanisms to lower blood pressure.

Topics: 6-Ketoprostaglandin F1 alpha; Aldosterone; Animals; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Drugs, Chinese Herbal; Endothelins; Female; Hypertension, Renovascular; Male; Random Allocation; Rats; Rats, Wistar; Thromboxane B2

Impaired contralateral kidney (CLK) function is important in the maintenance of hypertension in the two-kidney, one-clip (2K, 1C) Goldblatt rat model. Since glomerular filtration rate (GFR) is influenced by the products of arachidonic acid metabolism, we investigated the potential role of eicosanoids as mediators of impaired CLK pressure-volume regulation. At 4 wk following right renal artery clipping, GFR of hypertensive rats was significantly reduced. This decrease was due to the fixed reduction in GFR of the clipped kidney and failure of the CLK to increase its GFR. Thromboxane (Tx) production by isolated perfused CLK was significantly elevated, whereas prostacyclin production remained unchanged. Furthermore, CLK GFR was inversely proportional to Tx production. Treatment of 4-wk hypertensive animals with either the Tx synthase inhibitor UK-38,485 or the Tx receptor antagonist GR 32191 produced a significant increase in CLK GFR. In addition, treatment with either the Tx synthase inhibitor or the Tx receptor antagonist significantly reduced systemic blood pressure. Thus, in this 2K, 1C model of hypertension, increased renal Tx production prevents functional hypertrophy of the contralateral kidney. As a result, CLK pressure-volume regulation is impaired and systemic hypertension is maintained. Furthermore, Tx antagonists restore CLK function and acutely lower systemic blood pressure. Therefore, increased renal Tx production by the CLK appears to be an important mediator of hypertension in the 2K, 1C model.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Biphenyl Compounds; Blood Pressure; Glomerular Filtration Rate; Heptanoic Acids; Hypertension, Renovascular; Imidazoles; Kidney; Male; Rats; Rats, Inbred Strains; Receptors, Prostaglandin; Receptors, Thromboxane; Reference Values; Regional Blood Flow; Renal Circulation; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

A rat model combining two-kidney, one-clip (2K1C) renovascular hypertension and streptozotocin-induced diabetes mellitus was used to assess the pathogenetic significance of vasodilator prostaglandins in diabetic glomerular injury. Glomeruli isolated from normotensive diabetic rats produced greater than normal amounts of PGE2 and 6-keto PGF1 alpha under in vitro incubation conditions. In 2K1C hypertensive-diabetic rats, glomeruli from unclipped kidneys (which are prone to accelerated diabetic glomerular injury) produced similarly elevated amounts of PGE2 and 6-keto PGF1 alpha, which significantly exceeded the levels produced by glomeruli from clipped kidneys (which are relatively protected from glomerular injury), despite exposure to a similar diabetic environment. In contrast, glomeruli from both unclipped and clipped kidneys of 2K1C hypertensive-non-diabetic rats produced normal amounts of PGE2 and 6-keto PGF1 alpha. These results suggests a correlation between vasodilator prostaglandin metabolism and susceptibility to diabetic glomerular injury, and illustrate that enhanced glomerular prostaglandin production is not an invariable metabolic consequence of hyperglycemia or insulin deficiency. The data also demonstrate that hemodynamic as well as metabolic factors may influence glomerular prostaglandin metabolism in experimental diabetes mellitus.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dinoprostone; Hypertension, Renovascular; Kidney Glomerulus; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Renal Circulation

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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Creatinine; Dexamethasone; Dinoprostone; Disease Models, Animal; Hypertension, Renovascular; Male; Phospholipases A; Phospholipases A2; Potassium; Rats; Rats, Inbred Strains; Reference Values; Sodium; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antihypertensive Agents; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Dinoprostone; Hypertension, Renovascular; Phospholipases A; Phospholipids; Platelet Activating Factor; Prostaglandins E; Rats

The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219), an orally active angiotensin converting enzyme (ACE) inhibitor, on humoral factors which participated in the blood pressure control were examined with various experimental animals. In conscious renal hypertensive dogs, alacepril (3 mg/kg p.o.) showed decreases in plasma ACE activity and plasma aldosterone concentration, and increases in plasma renin activity and plasma angiotensin I concentration accompanied by a significant reduction in blood pressure. In conscious normotensive dogs, alacepril (1 and 3 mg/kg p.o.) showed an increase in urinary excretion of bradykinin accompanied by increases in urinary water and sodium excretion. In spontaneously hypertensive rats, alacepril (30 and 100 mg/kg p.o.) showed increases in urinary excretion of bradykinin and 6-keto-prostaglandin Fl alpha, and a decrease in that of aldosterone accompanied by increased in excretion of water and sodium. These results indicate that the antihypertensive activity of alacepril is due to the suppression of renin-angiotensin-aldosterone system and the enhancement of kallikrein-kinin-prostaglandin system through the inhibition of ACE (kininase II) activity in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Aldosterone; Angiotensin I; Animals; Antihypertensive Agents; Blood Pressure; Bradykinin; Captopril; Dinoprostone; Dogs; Hypertension; Hypertension, Renovascular; Kallikreins; Male; Peptidyl-Dipeptidase A; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Water-Electrolyte Balance

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)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Blood Pressure; Epoprostenol; Hypertension, Renovascular; Male; Platelet Activating Factor; Rats; Rats, Inbred Strains

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Female; Humans; Hypertension; Hypertension, Renovascular; Male; Middle Aged; Thromboxane B2

The contribution of the renal nerves in maintaining blood pressure and modulating renal prostanoid synthesis was examined in established (less than 8 wk in duration) one-kidney, one-clip (1K,1C) hypertension in the rat. Systolic blood pressure was measured for 7 days after renal denervation, at which time the renal artery clip was removed. Twenty-four-hour urinary excretion of PGE2 and 6-keto-PGF1 alpha (stable degradation product of PGI2) was determined before and after denervation and unclipping. Compared with sham-denervated rats, denervation (n = 15) resulted in a small but significant fall in blood pressure (from 216 +/- 4 to 182 +/- 4 mmHg after 48 h) and an increase in urinary 6-keto-PGF1 alpha (from 31 +/- 4 to 43 +/- 5 ng/24 h after 24 h). There was no change in PGE2 excretion. Seven days after surgery, blood pressures were similar in denervated (202 +/- 4 mmHg) and sham-denervated (211 +/- 5 mmHg) rats and fell to a similar extent 24 h after unclipping (142 +/- 3 and 147 +/- 4 mmHg, respectively). Urinary 6-keto-PGF1 alpha increased from 25 +/- 5 to 74 +/- 11 in denervated and 21 +/- 2 to 72 +/- 9 ng/24 h in sham-denervated rats in the 24 h after unclipping. PGE2 excretion increased approximately twofold over this period. These findings indicate that the renal nerves have only a minor role in established hypertension in the 1K,1C rat and that the reversal of hypertension and stimulation of renal prostanoid synthesis following unclipping is not dependent on neural mechanisms.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Denervation; Dinoprostone; Hypertension, Renovascular; Kidney; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Time Factors

To study the influence of dietary modification of prostaglandin synthesis on blood pressure regulation, the effects of dietary enrichment with linoleic acid were compared with standard rat chow in three groups of 24 rats before and after renal artery constriction and contralateral nephrectomy. Dietary supplementation with 40 energy% sunflower seed oil or linseed oil respectively caused incorporation of linoleic or linolenic acids into tissue phospholipids. Relative to the sunflower seed oil, the linseed oil diet led to inhibition of prostanoid synthesis in kidney, serum or aorta in vitro and urine in vivo. Rats on both oil-rich diets had lower blood pressures than rats on a standard diet. Thus, partial suppression of prostaglandin synthesis did not accelerate one-kidney, one clip Goldblatt hypertension, nor did sunflower oil protect against hypertension in a way that could be specifically ascribed to changes in prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; alpha-Linolenic Acid; Animals; Aorta; Blood Pressure; Body Weight; Dietary Fats; Fatty Acids; Hypertension, Renovascular; Kidney; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Prostaglandins; Rats; Thromboxanes

The 24 hour urinary excretion of 6-keto PGF1 alpha and PGE2 was compared in 2 kidney-1 clip rats developing hypertension within 12 weeks of renal artery clipping with rats remaining normotensive over this period. Although systolic blood pressure was markedly elevated in the hypertensive (210 +/- 5.1 mm Hg), in contrast with the normotensive (141 +/- 1.9 mm Hg) group, urinary levels of 6-keto PGF1 alpha (26.1 +/- 3.4 and 22.1 +/- 2.7 ng/24 h, respectively) and PGE2 (52.8 +/- 28 and 53.3 +/- 10.8 ng/24 h) were not significantly different. Treating the 2 kidney-1 clip normotensive group with indomethacin (3.0 mg/kg, by intraperitoneal injection) twice-weekly for 3 weeks reduced 6-keto PGF1 alpha excretion from 22.1 +/- 2.7 to 8.4 +/- 2.2 ng/24 h (P less than 0.002) and PGE2 from 53.3 +/- 10.8 to 8.7 +/- 1.8 ng/24 h (P less than 0.002) but did not change blood pressure when compared with a similar group given buffer vehicle only. These findings do not support a role for renal prostaglandins in 2 kidney-1 clip hypertension in the rat.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Epoprostenol; Hypertension, Renovascular; Indomethacin; Kidney; Male; Prostaglandins E; Rats; Time Factors

The release of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), by the perfused mesenteric arteries of renal and spontaneously hypertensive rats (SHR) have been measured. Unstimulated mesenteric arteries from two-kidney one-clip hypertensive rats (2K-1C) released 1.6 times as much PGE2 and 2.7 times as much 6-keto-PGF1 alpha as those of control rats. The release of PGE2 by mesenteric arteries from one-kidney one-clip hypertensive rats (1K-1C) was not significantly different from that of uninephrectomized normotensive rats, but the release of 6-keto-PGF1 alpha was 3.5 times higher in the former than in the latter. Norepinephrine (NE) induced a dose-related increase in perfusion pressure, in PGE2, and 6-keto-PGF1 alpha release in all four groups. However, its effect on the release of PGE2 was more pronounced in 2K-1C than in sham-operated rats. There was no difference between 1K-1C and the uninephrectomized group. The effect of NE on the release of 6-keto-PGF1 alpha was significantly higher for both renal hypertensive groups. These results indicate that the release of PGE2 is more dependent on the loss of renal mass than on hypertension, while the reverse applies to the release of 6-keto-PGF1 alpha. Unstimulated mesenteric arteries from SHR released less PGE2 and less 6-keto-PGF1 alpha than those of Wistar-Kyoto normotensive rats (WKY), but the release was not significantly different from Wistar rats. Under NE stimulation, WKY mesenteric arteries showed almost no increase in release of PGs. Compared with those of Wistar rats, SHR mesenteric arteries showed a greater pressor response to NE, a lower PGE2 release, and the same release of 6-keto-PGF1 alpha. These findings reveal the difficulty of selecting an appropriate control group in studies involving SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Arteries; Dose-Response Relationship, Drug; Hypertension; Hypertension, Renovascular; In Vitro Techniques; Male; Mesenteric Arteries; Norepinephrine; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains