Effects of thromboxane synthase inhibition on vascular responsiveness in the in vivo rat mesentery.

Jackson, Edwin K.

doi:10.1172/jci112238

Cited by 14 publications

(2 citation statements)

References 31 publications

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“…13 Moreover, the inhibition of thromboxane synthesis attenuates vascular responses to sympathetic nerve stimulation. 48 Increased TxB 2 synthesis stimulated by Ang II may have increased the release of, or responsiveness to, sympathetic neurotransmitters and thereby facilitated the development of hypertension. Thromboxane synthesis or receptor antagonists have been shown to reduce the systemic and renal vasoconstriction produced by short-term Ang II infusions 49 and to reduce the blood pressure of conscious rats receiving prolonged Ang II infusions.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

et al. 1989

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To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE 2 , prostacyclin derivative 6kPGF, a , and thromboxane [Tx] derivative TxB 2 ). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE 2 did not increase in angiotensin rats; however, both 6kPGF, a and TxB 2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 Mg/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF la or TxB 2 . Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG. {Hypertension 1989;14:396-403) A ngiotensin II (Ang II) is intimately involved in / \ the homeostatic regulation of blood pres-.Z \ . sure and body fluids, although the details of its mechanisms of action remain quite controversial. 1In addition to a well-characterized vasoconstrictor action, Ang II has also been proposed to increase peripheral vascular resistance indirectly through peripheral and central mechanisms that lead to an increased activity of the sympathetic nervous system.2 -4 Further, Ang II causes sodium retention both by a direct action on the renal tubule, 5 and through the stimulation of aldosterone release. 5Finally, Ang II administration influences the plasma concentration, renal excretion, and tissue generation of prostaglandins (PGs) that modulate the vasoconstriction.6 However, the relevance of some of these studies to the pathophysiological role of Ang II in hypertension is not clear, as many were conducted during short-term Ang II infusion in animals under anesthesia.To further define mechanisms in the production of Ang II-related hypertension, we infused Ang II into conscious rats over a 14-day period. We measured sympathetic nervous system activity directly with bipolar electrodes implanted on their splanchnic nerves. We determined the excretion of aldosterone and PG (PGE2, 6kPGFi a , and thromboxane [Tx]B 2 ). To further investigate the role of the s...

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Section: Discussionmentioning

confidence: 99%

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

et al. 1989

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“…On the 13th day after implantation of the mini-osmotic pump, five rats from groups I and II and five from groups III and IV were selected at random and prepared for in situ perfusion oftheir mesenteric vascular beds as described previously (4 ulation and exogenous norepinephrine were elicited and recorded as previously described (4). Two more groups of rats were pretreated for 1 wk with either normal drinking water (n = 7) or drinking water containing 0.1% caffeine (n = 20).…”

Section: Methodsmentioning

confidence: 99%

Caffeine enhances the slow-pressor response to angiotensin II in rats. Evidence for a caffeine-angiotensin II interaction with the sympathetic nervous system.

Ohnishi¹,

Li²,

Branch³

et al. 1987

J. Clin. Invest.

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The purpose of this study was to determine if caffeine augments the slow-pressor response to chronic low-dose infusions of angiotensin II (All) or the rapid-pressor response to acute infusions of All. All was infused (125 ng/min i.p.) for 12 d via miniosmotic pumps in four groups of rats: group I, intact rats not treated with caffeine (n = 9); group II, intact rats treated with caffeine (0.1% in dinking water, n = 9, group

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Increased bioavailability of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after portacaval shunting

et al. 1989

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Metabolites of arachidonic acid have been attributed to severe circulatory, metabolic and hormonal alterations in patients with chronic liver disease. In order to study changes of the tissue-specific availability of enzymes of eicosanoid synthesis, we used portacaval-shunted rats, as this model exhibits many clinical and biochemical similarities to patients suffering from cirrhosis of the liver. Microsomal mass and maximal velocity of prostaglandin H synthase, the initial enzyme of prostaglandin synthesis, were markedly and permanently increased after shunting in both hepatic and extrahepatic tissues as compared to those of sham-operated rats. Maximal velocity of thromboxane synthase and prostacyclin synthase, two more peripheral enzymes of the arachidonic acid cascade, were tissue-specifically enhanced, whereas the apparent affinities (Km) remained unchanged. Determination of 5-lipoxygenase activity in tissue preparations disclosed a preferential increase in the liver, lung and renal cortex after portacaval shunting. Furthermore, exposure to endotoxin closely mimicked the shunting-induced changes. These results suggest that after portacaval shunting and possibly in patients with advanced liver disease, profound abnormalities at the level of local enzyme expression might play a pathophysiologically important role in the control of eicosanoid synthesis.

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Effects of thromboxane synthase inhibition on vascular responsiveness in the in vivo rat mesentery.

Abstract: The purpose of this investigation was to determine the effects of thromboxane synthase inhibition on vascular responsiveness. To

Cited by 14 publications

References 31 publications

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

Caffeine enhances the slow-pressor response to angiotensin II in rats. Evidence for a caffeine-angiotensin II interaction with the sympathetic nervous system.

Increased bioavailability of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after portacaval shunting

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