A physico-chemical comparison of aortic receptors in rat hypertension models

Meyer, Walter J.; Nichols, Nancy R.; Nguyen, Hanh H.

doi:10.1016/0024-3205(86)90183-9

Cited by 2 publications

(2 citation statements)

References 12 publications

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“…It is well established that there are significant differences in the vascular biology of these different rat strains. 34,35 Furthermore, there are differences in the vascular phenotype expression with aging between the strains. 36 One of the seminal features of the aging vasculature is an increase in arterial stiffness, which is additionally exacerbated by hypertension and diabetes.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Arginase I Restores NO Signaling in the Vasculature of Old Rats

et al. 2006

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Abstract-Arginase, expressed in endothelial cells and upregulated in aging blood vessels, competes with NO synthase (NOS) for L-arginine, thus modulating vasoreactivity and attenuating NO signaling. Moreover, arginase inhibition restores endothelial NOS signaling and L-arginine responsiveness in old rat aorta. The arginase isoform responsible for modulating NOS, however, remains unknown. Because isoform-specific arginase inhibitors are unavailable, we used an antisense (AS) oligonucleotide approach to knockdown arginase I (Arg I). Western blot and quantitative PCR confirmed that Arg I is the predominant isoform expressed in endothelialized aortic rings and is upregulated in old rats compared with young. Aortic rings from 22-month-old rats were incubated for 24 hours with sense (S), AS oligonucleotides, or medium alone (C). Immunohistochemistry, immunoblotting, and enzyme assay confirmed a significant knockdown of Arg I protein and arginase activity in AS but not S or C rings. Conversely, calcium-dependent NOS activity and vascular metabolites of NO was increased in AS versus S or C rings. Acetylcholine (endothelial-dependent) vasorelaxant responses were enhanced in AS versus S or C treated rings. In addition, 1H-oxadiazolo quinoxalin-1-one (10 mol/L), a soluble guanylyl cyclase inhibitor, increased the phenylephrine response in AS compared with S and C rings suggesting increased NO bioavailability. Finally, L-arginine (0.1 mmol/L)-induced relaxation was increased in AS versus C rings. These data support our hypothesis that Arg I plays a critical role in the pathobiology of age-related endothelial dysfunction. AS oligonucleotides may, therefore, represent a novel therapeutic strategy against age-related vascular endothelial dysfunction.

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Section: Discussionmentioning

confidence: 99%

Knockdown of Arginase I Restores NO Signaling in the Vasculature of Old Rats

et al. 2006

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“…Moreover, F344 strain is resistant to salt-and mineralocorticoid-induced hypertension [7][8][9]. The aortic corticoid receptors I of F344 have a lower affinity to aldosterone compared with that of salt-sensitive WKY rats [10,11]. Taken together, these data suggest a different state of the RAS in F344 strain compared with other strains, with consequences at the level of the arterial system.…”

mentioning

confidence: 98%

Different vascular responsiveness to angiotensin II in two normotensive rat strains

Herin

Blanc

Basset

et al. 2003

Fundamemntal Clinical Pharma

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Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin-angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose-response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800 microL/min, i.v.) were used to reflect arterial wall structure. The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37 +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.

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A physico-chemical comparison of aortic receptors in rat hypertension models

Cited by 2 publications

References 12 publications

Knockdown of Arginase I Restores NO Signaling in the Vasculature of Old Rats

Knockdown of Arginase I Restores NO Signaling in the Vasculature of Old Rats

Different vascular responsiveness to angiotensin II in two normotensive rat strains

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