In vivo administration of KCNQ channel modulators influences blood pressure and mesenteric vascular resistance in rats

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

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Antenatal betamethasone has a sex-dependent effect on the in vivo response to endothelin in adult sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00579.2012 ◽

2013 ◽

Vol 304 (8) ◽

pp. R581-R587 ◽

Cited By ~ 8

Author(s):

Jeong-Heon Lee ◽

Jie Zhang ◽

Lourdes Flores ◽

James C. Rose ◽

G. Angela Massmann ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Resistance ◽

Femoral Artery ◽

Resistance Response ◽

Adult Sheep ◽

Endothelin System ◽

Pregnant Sheep ◽

Vascular Catheters ◽

Artery Flow

Antenatal steroid administration is associated with multiple cardiometabolic alterations, including hypertension; however, the mechanisms underlying this phenomenon are unclear. The aim of the present study was to ascertain, in vivo, the contribution of the endothelin system to the development of hypertension in the adult offspring and the signaling pathway involved. Pregnant sheep were treated with two doses of betamethasone ( n = 23) or vehicle ( n = 22) at 80 days (∼0.55) gestation and allowed to deliver at term. Adult sheep were chronically instrumented under general anesthesia to place vascular catheters and a femoral artery flow probe. Blood pressure and flow were recorded continuously, and femoral artery vascular resistance was calculated before and during administration of endothelin 1 (ET-1). Selective blockers (dantrolene, BQ123, niacinamide) or saline were administered simultaneously. Betamethasone-exposed animals exhibited a significant elevation in mean blood pressure (female: 98 ± 1.8 vs. 92 ± 2.1; males: 97 ± 3.4 vs. 90 ± 2.3; mmHg; P < 0.05). ET-1 elicited a significant increase in blood pressure ( F = 56.4; P < 0.001) and in vascular resistance ( F = 44.3; P < 0.001) in all groups. A betamethasone effect in the vascular resistance response to ET-1 ( F = 25.7; P < 0.001) was present in females only, and the effect was partially blunted by niacinamide ( F = 6.6; P < 0.01). Combined administration of niacinamide and BQ123, as well as of dantrolene abolished the betamethasone effect on vascular resistance. No significant differences in mRNA expression of ETA or ETB in endothelial or smooth muscle cells of resistance-size arteries were observed. We conclude that the betamethasone effect on vascular resistance is mediated by an enhanced response to ET-1 through ETA receptor via the cyclic ADPR/ryanodine pathway.

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In vivo administration of d-arginine: effects on blood pressure and vascular function in angiotensin II-induced hypertensive rats

Atherosclerosis ◽

10.1016/j.atherosclerosis.2004.05.016 ◽

2004 ◽

Vol 176 (2) ◽

pp. 219-225 ◽

Cited By ~ 5

Author(s):

Gerald Wölkart ◽

Heike Stessel ◽

Friedrich Brunner

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Vascular Function ◽

Hypertensive Rats ◽

In Vivo Administration

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Physical and adrenergic factors affecting systemic vascular resistance in the rainbow trout: a comparison with branchial vascular resistance

Journal of Experimental Biology ◽

10.1242/jeb.63.2.505 ◽

1975 ◽

Vol 63 (2) ◽

pp. 505-523

Author(s):

C. M. Wood ◽

G. Shelton

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Plasma Catecholamines ◽

Factors Affecting ◽

Adrenergic Control ◽

Sympathetic Nervous ◽

Catecholamine Levels

The passive distensibility and adrenergic reactivity of the systemic vascular resistance (Rs) in Salmogairdneri have been studied using perfused trunk preparations, and the data compared with previous results on the branchial resistance (Rg). At normal levels of efferent blood pressure, Rs is relatively more distensible than Rg in response to afferent pressure increases, but this difference may not be important in vivo. alpha-adrenegic constrictory receptors predominate in Rs, in contrast to beta-adrenergic dilatory receptors in Rg; a significant alpha-adrenergic tone in Rs is lost during perfusion. Rs is far less sensitive than Rg to circulatory catecholamine levels. It is suggested that the sympathetic nervous system, rather than plasma catecholamines, provides the effective adrenergic control of Rs in vivo.

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Chronic In Vivo Administration of MnTnBuOE-2-PyP5+ Does Not Decrease Hypertensive Blood Pressure

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2020.10.249 ◽

2020 ◽

Vol 159 ◽

pp. S97

Author(s):

Sarah Schlichte ◽

Elizabeth Kosmacek ◽

Rebecca Oberley-Deegan ◽

Matthew Zimmerman

Keyword(s):

Blood Pressure ◽

In Vivo Administration

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Vasoconstrictor actions of atrial natriuretic peptide in the splanchnic circulation of anesthetized dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.6.r1822 ◽

1998 ◽

Vol 275 (6) ◽

pp. R1822-R1832 ◽

Cited By ~ 2

Author(s):

Robyn L. Woods

Keyword(s):

Blood Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Vascular Resistance ◽

Femoral Vein ◽

Rate Of Change ◽

Maximum Increase ◽

Anesthetized Dogs ◽

Atrial Natriuretic

Intravenous atrial natriuretic peptide (ANP) usually results in splanchnic vasoconstriction in humans or experimental animals that is accompanied by falls in blood pressure and/or cardiac output. To determine direct in vivo effects in the present study, ANP was infused (12 ng ⋅ kg−1 ⋅ min−1) directly into the mesenteric (iMA) and hepatic (iHA) arterial beds of anesthetized dogs, thereby minimizing changes in blood pressure. Over the first 2 min of iMA infusion, rate of change in mesenteric vascular resistance was 19.6 ± 5.4 mmHg ⋅ l−1 ⋅ min−1/min, reaching a maximum increase in resistance of 22 ± 4% compared with baseline after ∼10 min. There was no evidence of vasodilatation at any stage. The mesenteric response was similar whether ANP was infused iMA, iHA, or via the femoral vein (30 ng ⋅ kg−1 ⋅ min−1). In contrast, hepatic vasoconstrictor response to ANP infusion iHA or into the portal vein was only evident after ∼5 min, reaching a maximum increase in hepatic vascular resistance of 11 ± 6% after ∼15 min iHA infusion. When preinfused through the gut vasculature (iMA), ANP increased hepatic vascular resistance earlier and reached similar levels (14 ± 3%), despite a lower arterial concentration of ANP. It is proposed that a vasoconstrictor agent from the intestinal circulation contributed to ANP-induced splanchnic vasoconstriction.

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Aldosterone: Refreshing a Slow Hormone by Swift Action

Physiology ◽

10.1152/nips.01596.2003 ◽

2004 ◽

Vol 19 (3) ◽

pp. 97-100 ◽

Cited By ~ 3

Author(s):

Brigitte Boldyreff ◽

Martin Wehling

Keyword(s):

Blood Pressure ◽

Vascular Resistance ◽

Sodium Transport ◽

Clinical Importance ◽

In Vivo Studies ◽

Target Cells ◽

Peripheral Vascular ◽

Genomic Effects ◽

Nongenomic Effects

Aldosterone elicits not only genomic effects with physiological consequences within hours or days but also elicits rapid nongenomic effects, such as activation of sodium transport in target cells, within seconds or minutes. Rapid aldosterone effects, which have also been shown in several in vivo studies in humans (e.g., increase in peripheral vascular resistance and blood pressure), are of potential clinical importance.

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Passive autoregulation of portal venous pressure: distensible hepatic resistance

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.263.5.g702 ◽

1992 ◽

Vol 263 (5) ◽

pp. G702-G708 ◽

Cited By ~ 2

Author(s):

W. W. Lautt ◽

D. J. Legare

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Vascular Resistance ◽

Venous Pressure ◽

Portal Pressure ◽

Portal Blood Flow ◽

Minor Effect ◽

Basal Resistance ◽

Resistance Vessels

Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined.

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