Alpha 1 adrenergic receptor control of renal blood vessels during aging

Passmore, John C.; Rowell, P.; Joshua, Irving G.; Porter, James P.; Patel, Divyan H; Falcone, John L.

doi:10.1139/y05-015

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…General transcription inhibitor actinomycin D, but not translational inhibitor cycloheximide, abolished the DSPinduced depressed contraction to norepinephrine, indicating that a transcriptional mechanism is responsible for this downregulation. It has been demonstrated that, in rat mesenteric artery, norepinephrine induces vasoconstriction mainly via α 1A -adrenoceptor receptor [10,15]. This is well in line with our findings that the DSP-induced depressed contractile response to norepinephrine links with the decrease in α 1Aadrenoceptor mRNA expression in the smooth muscle, but not α 2 -adrenoceptor.…”

Section: Discussionsupporting

confidence: 92%

Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Zhang

Cao

et al. 2007

Basic Clin Pharma Tox

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Smoking is a strong risk factor for cardiovascular disease that is a leading cause of death and disability in Western countries. The present study was designed to investigate the effect of lipid-soluble smoke particles (DSP) on α -adrenoceptor expression in organ culture of rat mesenteric arteries and human epiploon arteries. Myograph and real-time reverse transcription-polymerase chain reaction were employed to assess vascular smooth muscle contractibility and the receptor mRNA expression in the smooth muscle cells. Organ culture of the arterial segments in the presence of DSP (0.2 µ l/ml) resulted in a significantly decreased contractile response to norepinephrine, compared to control (i.e. in the presence of dimethyl sulfoxide) (P < 0.05). This was in parallel with a down-regulation of α 1A -adrenoceptor mRNA expression in the smooth muscle, while α 2 -adrenoceptor mRNA expression remained unchanged. General transcription inhibitor actinomycin D (10 -5.4 M), but not the translational inhibitor cycloheximide (10 -5 M), significantly abolished the DSP-induced depressed contraction to norepinephrine. IMD-0354 (10 -7.5 M), a specific nuclear factor-κ B (NF-κ B) pathway inhibitor, markedly reversed the DSP-induced down-regulation of α 1A -adrenoceptor expression in the smooth muscle at both functional and mRNA levels. Thus, we have demonstrated that smoking-induced down-regulation of α 1A -adrenoceptor expression was via the transcriptional factor NF-κ B pathway.Epidemiological studies have shown that there are strong links between cardiovascular disease and cigarette smoking, including secondhand smoking [1]. Smoking per se has been reported to result in 5 million premature deaths per year worldwide, and the majority of these are due to cardiovascular events [2]. Smoking is believed to cause damage to arterial wall with dysfunction of the endothelium and smooth muscle cells, and subsequently enhance atherosclerotic plaque formation [3]. However, the molecular mechanisms behind this process are still largely unknown.Previous studies showed that lipid-soluble smoke particles (DSP) cause damage to vascular endothelial cells (VEC) and vascular smooth muscle cells (VSMC) [4]; reduce the release of pro-stacyclin from VEC [5,6], and increase 125 I-low density lipoprotein (LDL) uptake by VSMC. In addition, we have recently demonstrated that DSP reduced endotheliumdependent dilatation in rat mesenteric arteries and human middle cerebral arteries [7], and resulted in up-regulation of endothelin type A and B (ET A and ET B ) receptors in the smooth muscle of rat mesenteric arteries [8] and rat bronchi [9].Adrenoceptor belongs to G-protein-coupled receptors (GPCRs) family. In the vasculature, adrenoceptor, particularly α -adrenoceptor, has been demonstrated to play important roles in regulating blood flow and blood pressure by altering artery resistance in cardiovascular disease [10]. Experimental and clinical studies showed that there is an increased α -adrenoceptor-mediated vasoconstriction in hypertensive patien...

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Section: Discussionsupporting

confidence: 92%

Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Zhang

Cao

et al. 2007

Basic Clin Pharma Tox

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“…Previous publications from our laboratories Passmore et al, 2005] reveal that both Wistar and Munich Wistar rat interlobar arteries show similar age-and gender-related changes in interlobar artery contraction. Figure 1 provides an overall synopsis of species, gender, and age concepts for interlobar artery contraction.…”

Section: Adrenergic Control Of the Renal Circulationmentioning

confidence: 61%

“…The alpha-1 A receptor is the predominant alpha-1 adrenergic receptor subtype, which mediates vasoconstrictor responses to exogenously administered norepinephrine in the perfused kidney of the adult rat [Blue et al, 1995;Passmore et al, 2005].…”

Section: Adrenergic Control Of the Renal Circulationmentioning

confidence: 99%

Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging

Passmore

Joshua

Rowell

et al. 2005

J of Cellular Biochemistry

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As human males age, a decline in baroreflex-mediated elevation of blood pressure occurs due, at least in part, to a reduction in alpha-1 adrenergic vasoconstrictor function. Alpha adrenergic constriction is mediated by guanosine triphosphate binding Protein (G Protein) coupled signaling pathways. Alpha-1 A/C, B, and D adrenergic receptor expressions, measured by GeneChip array, are not reduced during aging in renal blood vessels of male or female rats. Alpha-1 A GeneChip expression is greater, at all ages studied, in females than in males. Prazosin binding by alpha-1 adrenergic receptors is greater in young adult female rats than in young adult male rats; however, it is reduced with aging in both male and female rats. G alpha q GeneChip expression declines while expression of adrenergic receptor kinase (GRK2) and tyrosine phosphatases (TyrP) increase with aging in male rats. The declines in alpha-1 adrenergic receptor binding and G alpha q expression and also the increases in GRK2 and TyrP expression likely relate to the age-related decline of vasoconstriction in male rats. The information that the expression of alpha-1 A adrenergic receptors is greater in female rats and (GRK2) expression does not increase during aging could relate to the gender differences in vasoconstrictor function with aging. Gene therapy to ameliorate the age-related decline in renal function could possibly reduce the need for renal dialysis. Signaling pathways such as those reviewed herein may provide an outline of the molecular pathways needed to move toward successful renal gene therapy for aging individuals.

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“…In human males, a marked decline in baroreflex buffering of blood pressure is due to, at least in part, a marked reduction in a-adrenergic receptor function (Castellani et al 1999;Jones et al 2003). Speculation on how these findings could be reconciled might include: 1) a comparison of prazosin binding in the rat parotid cell indicating a naturally occurring post-a-adrenergic receptor defect in signal transduction (Ishikawa et al 1989); 2) Age-related impairments in a-adrenergic responsiveness could be partially caused by alterations in the coupling of a-adrenergic receptors and G-proteins (Myamoto et al 1992); 3) A decline in the G protein amplification of constriction (Robert et al 1998) and 4) Competitive binding experiments (prazosin) revealed that maximal binding of the a-adrenergic receptor of the interlobar arteries is reduced 25% by 10 months of age and 50% by 18 months of age (Passmore et al 2005). We speculate that the a-adrenergic receptor density or downstream signaling (specifically the G-protein cascade) events are altered as a function of age in the male rat; pointing to the possibility that the a-adrenergic receptors are down-regulated (Parekh et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Decreased alpha-adrenergic constriction of renal preglomerular arteries occurs with age and is gender-specific in the rat

Falcone

Joshua

Passmore

2005

AGE

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Age and/or gender appear to moderate alpha-adrenergic mediated constrictor mechanisms found in the interlobar arteries of the Munich Wistar rat. We have determined the extent of constriction to alpha-adrenergic receptor stimulation using norepinephrine, phenylephrine and A61603 (a 1A -adrenergic receptor agonist) as a function of age and gender. Norepinephrine produced less constriction in male-derived arteries at ages greater than eight months as compared to the younger adult male (four to six months). The arteries derived from females did not demonstrate altered constriction until greater than 15 months of age. Similarly, arteries derived from the male demonstrated weaker constrictions to phenylephrine (10 j6 to 10 j3 M) at ages greater than eight months while arteries from females showed differences at greater than 15 months. In contrast, the effective concentration of norepinephrine to cause a 50% maximal constriction (EC 50 ) was significantly less in the four to five-month-old male rats compared to the pooled data from older groups. Interestingly, four to five month old males had A61603 EC 50 values similar to the 8-to 12-month and 15+ old females. These studies conclude that an age related loss of sympathetic a-adrenergic constriction of renal interlobar arteries is present in Munich Wistar rats. Furthermore, this loss, while similar along longitudinal aspects of age, is also different as a function of gender with the loss of a-adrenergic constrictor function delayed in the female when compared to the male.

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Alpha 1 adrenergic receptor control of renal blood vessels during aging

Cited by 7 publications

References 21 publications

Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging

Decreased alpha-adrenergic constriction of renal preglomerular arteries occurs with age and is gender-specific in the rat

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Alpha 1 adrenergic receptor control of renal blood vessels during aging

Cited by 7 publications

References 21 publications

Down‐Regulation of α1‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Down‐Regulation of α1‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging

Decreased alpha-adrenergic constriction of renal preglomerular arteries occurs with age and is gender-specific in the rat

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Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway

Down‐Regulation of α₁‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway