Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Wu, Xiao Chun; Johns, Edward J.; Michael, J.; Richards, Nicholas T.

doi:10.1111/j.1476-5381.1994.tb13080.x

Cited by 20 publications

(17 citation statements)

References 41 publications

(47 reference statements)

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“…This difference in PE sensitivity was endothelium-dependent, since removal of endothelium abolished the difference. Endothelium-dependent a-adrenergic constriction in arteries can be modulated by the NO and cyclooxygenase pathways [39]. To investigate the mechanisms by which PE sensitivity was increased in parous rats, we blocked these pathways with l-NAME and meclofenamate respectively.…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of repeated pregnancies (multiparity) on blood pressure regulation

Dhawan

Brookes

Kaufman

2004

Cardiovascular Research

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Objective: Pregnancy is associated with profound alterations in the cardiovascular system, the long-term effects of which are unknown. Human epidemiological studies suggest that multiparity (multiple pregnancies) increases the risk of cardiovascular disease. The mechanisms underlying these findings remain to be elucidated. The objective of this study was to determine the long-term effects of parity on cardiovascular regulation. Methods: Pressor responses to phenylephrine (PE) and acute stress were compared in conscious age-matched repeatedly breed (RB) and virgin rats. Vascular compliance and reactivity of isolated resistance-sized mesenteric arteries were studies using pressure and wire myograph. Results: We found that both exogenous PE and acute stress elicited greater pressor responses in RB than in aged-matched virgins. Pressure and wire myography also revealed that small mesenteric arteries from RB rats were less compliant than those from virgins (RB: 0.24F0.04 Mm mm Hg À1 , n=6 vs. virgins: 0.63F0.06 Am mm Hg À1 , n=6; pV0.05) and were more sensitive to PE (EC 50 RB: 1.58F0.08Â10 À6 M, n=10 vs. virgins: 2.05F0.09Â10 À6 M, n=14; pV0.05). Removal of the endothelium abolished the difference in sensitivity. More specifically, the augmented vascular response of RB was both nitric oxide (NO) and cyclooxygenase dependent. By contrast, there was no difference in methacholine-induced vasodilation of phenylephrine-preconstricted vessels. Conclusion: Our results suggest that repeated pregnancies induce long-term alterations in cardiovascular regulation due to changes in vascular compliance and endothelium-dependent vasoconstriction. We propose that such changes might influence the risk for cardiovascular disease in multiparous women.

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Section: Discussionmentioning

confidence: 99%

Long-term effects of repeated pregnancies (multiparity) on blood pressure regulation

Dhawan

Brookes

Kaufman

2004

Cardiovascular Research

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“…Prostaglandins are one of those endothelial factors involved in vascular control, and we observed a diminished contraction to KCl in both groups pretreated with indomethacin. The effects of blockade of prostaglandins on MRA contractile responses appears to be dependent on the protocol used to test the responses; whereas an increased effect of indomethacin after a single dose of KCl was reported (41), a detailed study of the dependence of contractile responses of rat MRA on cyclooxygenase products indicated that indomethacin decreased contraction to a dose response curve of KCl (42). These effects appear to be mediated by cyclooxygenase as well as lipooxygenase vasoconstrictor products released during contraction to KCl (42).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of blockade of prostaglandins on MRA contractile responses appears to be dependent on the protocol used to test the responses; whereas an increased effect of indomethacin after a single dose of KCl was reported (41), a detailed study of the dependence of contractile responses of rat MRA on cyclooxygenase products indicated that indomethacin decreased contraction to a dose response curve of KCl (42). These effects appear to be mediated by cyclooxygenase as well as lipooxygenase vasoconstrictor products released during contraction to KCl (42). Our results suggest involvement of vasoconstrictor prostanoids in KCl contraction, in agreement with previous findings on the effects of prostanoids on adrenergic contraction in rat arteries (43;44).…”

Section: Discussionmentioning

confidence: 99%

Increased Constrictor Tone Induced by Ouabain Treatment in Rats

Pulgar

Jeffers

Rashad

et al. 2013

Journal of Cardiovascular Pharmacology

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Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after long-term treatment with ouabain. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with ouabain (Oua, ~25 μg·day−1) or placebo for 8 weeks. Blood pressure increased in ouabain-treated animals, reaching 30% above baseline SBP after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRA) by wire myography. Contraction to potassium chloride (KCl) in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine (PE) and relaxation to acetylcholine (ACh) were similar between groups with a lower response to sodium nitroprusside (SNP) in Oua-treated arteries. Sensitivity to endothelin-1 (ET-1) was higher in Oua-treated arteries. Na+-K+ ATPase activity was decreased in MRA from Oua-treated animals, whereas protein expression of the Na+-K+-ATPase α2 isoform was increased in heart and unchanged in mesenteric artery. Pre-incubation with indomethacin (10−5M) or L-NAME (10−4M) abolished the differences in KCl response and Na+-K+ ATPase activity. Changes in MRA are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.

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“…Normally, NO synthase inhibition causes a leftward shift in the concentration-response curve and an increased maximal response. 52 These effects are absent in the arteries investigated in this study, meaning that the NO production under basal conditions (for example, without agonist-induced stimulation) is blunted. None of the treatments could restore the L-NAME induced leftward shift and only hydralazine restored the increase in maximal contraction induced by L-NAME.…”

Section: Discussionmentioning

confidence: 65%

“…25,52 Again, this shift was completely absent in vehicle-, losartan-or hydralazine-treated groups. After 4 weeks of chronic dual NEP/ECE inhibition, however, L-NAME caused a significant leftward shift.…”

Section: Discussionmentioning

confidence: 94%

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

et al. 2017

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Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine. We then compared effects of inhibition of NO synthase (NOS) (100 μM L-NAME), blockade of ET A -and ET B -receptors (10 μM bosentan) and stimulation of the endothelium with 0.001-10 μM acetylcholine (ACh) in isolated third-order mesenteric resistance arteries. Losartan and hydralazine significantly lowered blood pressure. Losartan decreased the media-to-lumen ratio of resistance arteries. L-NAME (1) increased arterial contractile responses to K + (5.9-40 mM) in the losartan, SOL1 and vehicle group and (2) increased the sensitivity to phenylephrine (PHE; 0.16-20 μM) in the SOL1 group but not in the losartan, hydralazine and vehicle group. Relaxing responses to ACh in the absence or presence of L-NAME during contractions induced by either 10 μM PHE or 40 mM K + were not altered by any in vivo treatment. Acute treatment with bosentan did, however, significantly improve maximal relaxing responses involving endothelium-derived nitric oxide and -hyperpolarizing factors in the SOL1 group but not in the losartan, hydralazine or vehicle group. Thus, chronic inhibition of NEP/ECE improved basal endothelial function but did not alter blood pressure, resistance artery structure and stimulated endothelium-dependent relaxing responses in 32-week-old SHR.

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Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Cited by 20 publications

References 41 publications

Long-term effects of repeated pregnancies (multiparity) on blood pressure regulation

Long-term effects of repeated pregnancies (multiparity) on blood pressure regulation

Increased Constrictor Tone Induced by Ouabain Treatment in Rats

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

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