Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

Kang, Kyu Tae; Sullivan, Jennifer C.; Sasser, Jennifer M.; Imig, John D.; Pollock, Jennifer S.

doi:10.1161/01.hyp.0000259669.40991.1e

Cited by 44 publications

(39 citation statements)

References 56 publications

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“…However, both unchanged and impaired acetylcholine-induced vasorelaxation have been observed to occur in small mesenteric arteries from hypertensive rats in various experimental hypertension models such as DOCA salt, SHR, and ANG rats. Therefore, NO bioavailability in resistance arteries may be different from that observed in conduit vessels (26).…”

Section: Hypertension and Endothelial Dysfunctionmentioning

confidence: 94%

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

Pereira

Paulo

Araújo

et al. 2011

Braz J Med Biol Res

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During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca 2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

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Section: Hypertension and Endothelial Dysfunctionmentioning

confidence: 94%

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

Pereira

Paulo

Araújo

et al. 2011

Braz J Med Biol Res

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“…Thoracic aorta and third‐order mesenteric artery segments were isolated and prepared for vascular reactivity experiments, as previously described 37. Cumulative concentration‐responses to phenylephrine were generated and normalized to the maximum constriction elicited by 100 mmol/L KCl.…”

Section: Methodsmentioning

confidence: 99%

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Fox

Becker

Loria

et al. 2018

JAHA

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BackgroundAcute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.Methods and ResultsAdult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in both genotypes; however, this response was significantly blunted in vascular endothelium‐specific ET‐1 knockout mice compared with control mice that were homozygous for the floxed allele. In mice pretreated for 3 days with the endothelin A antagonist, ABT‐627, or the dual endothelin A/B receptor antagonist, A‐182086, the pressor response to CSS was similar between genotypes. CSS significantly increased plasma ET‐1 levels in control mice that were homozygous for the floxed allele. CSS failed to elicit an increase in plasma ET‐1 in vascular endothelium‐specific ET‐1 knockout mice. Telemetry frequency domain analyses suggested similar autonomic responses to stress between genotypes, and isolated resistance arteries demonstrated similar sensitivity to α1‐adrenergic receptor‐mediated vasoconstriction.ConclusionsThese findings specify that acute stress‐induced activation of endothelium‐derived ET‐1 and subsequent endothelin A receptor activation is a novel mediator of the blood pressure response to acute psychosocial stress.

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“…Indeed, in some studies endothelium-dependent relaxation of resistance arteries has been reported to be preserved in hypertension by an NOS-dependent mechanism (Kang et al, 2007). Other studies have shown that abnormal endothelial function in small blood vessels does not predict cardiovascular events in patients with essential hypertension (Rizzoni et al, 2006) and indeed such dysfunction appears to be independent of vascular structural changes in hypertension (Rizzoni et al, 1998).…”

Section: Arterial Contractility and Hypertensionmentioning

confidence: 99%

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

Little

Cartwright

Neyses

et al. 2016

Pharmacology & Therapeutics

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The incidence of hypertension, the major modifiable risk factor for cardiovascular disease, is increasing. Thus, there is a pressing need for the development of new and more effective strategies to prevent and treat hypertension. Development of these relies on a continued evolution of our understanding of the mechanisms which control blood pressure (BP). Resistance arteries are important in the regulation of total peripheral resistance and BP; changes in their structure and function are strongly associated with hypertension. Anti-hypertensives which both reduce BP and reverse changes in resistance arterial structure reduce cardiovascular risk more than therapies which reduce BP alone. Hence, identification of novel potential vascular targets which modify BP is important. Hypertension is a multifactorial disorder which may include a genetic component. Genome wide association studies have identified ATP2B1, encoding the calcium pump plasma membrane calcium ATPase 1 (PMCA1), as having a strong association with BP and hypertension. Knockdown or reduced PMCA1 expression in mice has confirmed a physiological role for PMCA1 in BP and resistance arterial regulation. Altered expression or inhibition of PMCA4 has also been shown to modulate these parameters. The mechanisms whereby PMCA1 and 4 can modulate vascular function remain to be fully elucidated but may involve regulation of intracellular calcium homeostasis and/or comprise a structural role. However, clear physiological links between PMCA and BP, coupled with experimental studies directly linking PMCA1 and 4 to changes in BP and arterial function, suggest that they may be important targets for the development of new pharmacological modulators of BP.

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Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

Cited by 44 publications

References 56 publications

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

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