Alpha 1 adrenergic receptor control of renal blood vessels during aging

2005 ◽  
Vol 83 (4) ◽  
pp. 335-342 ◽  
Author(s):  
John C Passmore ◽  
Peter P Rowell ◽  
Irving G Joshua ◽  
James P Porter ◽  
Divyan H Patel ◽  
...  

Aging humans and rats have a reduced renal vascular constriction response to stress, change in posture, or exercise. In this study, renal interlobar arteries from 9- (intermediate age) to 15-month-old (aging) male Wistar rats constricted less to alpha-adrenergic agonists than those of 4-month-old (young adult) rats. The reduced contraction to A61603 (alpha 1 A agonist) was similar to that to norepinephrine and phenylephrine. Therefore, it appears that the reduction in constriction is primarily related to alpha 1 A receptor stimulation. GeneChip microarray hybridization analysis of the interlobar arteries with the RAE 230A GeneChip indicated that there were no significant differences in gene expression for alpha 1 A/C, 1B, or 1D receptors between 4-month-old (young adult) and 1-year-old (aging) male Wistar rats. Competitive binding experiments (prazosin) revealed that maximal binding (Bmax, fmol/mg protein) of the alpha 1 receptors of interlobar arteries was reduced 25% by 10 months of age and 50% by 18+ months of age. Alpha 1 receptor-induced arterial constriction and prazosin binding were both down-regulated. The loss of receptor-initiated constriction likely includes down-regulation of maximum agonist binding by alpha 1 adrenergic receptors.Key words: kidney, stress, blood flow, male vs. female, GeneChip array, prazosin.

Diabetology ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 190-204
Author(s):  
Ahmed Al-Humadi ◽  
Athina Strilakou ◽  
Hussam Al-Humadi ◽  
Rafal Al-Saigh ◽  
Emmanouel Agapitos ◽  
...  

Choline (Ch) is an essential molecule of substantial importance for the optimal development and function of several biological systems. Ch deprivation has been linked with abnormal fat metabolism, insulin resistance, and myocardial dysfunction. The current study provides evidence of an exacerbation of streptozotocin-induced cardiomyopathy in adult diabetic Wistar rats by dietary Ch deprivation through the administration of a Ch-deprived diet (CDD). Twenty-four adult male Wistar rats were randomly separated into four groups: control, diabetic (DM), choline-deprived through choline-deprived diet (CD), and diabetic choline-deprived (DM + CD). After five weeks of dietary intervention, myocardium echocardiographic and histological assessments were performed. Choline-deprived diabetic rats exhibited significantly slower heart rate, significantly higher myocardial ejection velocity and left ventricle wall tension index with a concomitant significant decreased LV posterior wall thickness as compared to diabetic rats fed on a standard diet. Moreover, histopathological evidence demonstrated an exacerbation of myocardial inflammation and fibrosis associated with significant up-regulation of VEGF expression in the diabetic rat myocardium as a result of Ch deprivation. The study’s findings are of particular significance since the examined experimental approach introduces a previously uncharacterised comorbidity simulation with regards to myocardial structure and functional profiling.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Carla S Ceron ◽  
Elen Rizzi ◽  
Danielle A Guimaraes ◽  
Alisson Martins-Oliveira ◽  
Raquel F Gerlach ◽  
...  

Nebivolol and metoprolol are β1-adrenergic receptor blockers with different properties. We hypothesized that nebivolol, but not metoprolol, could attenuate prooxidant and profibrotic mechanisms of hypertension vascular remodeling. Hypertension was induced in male Wistar rats by clipping the left renal artery. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (Nebi 10 mg/kg/day), metoprolol (Meto 20 mg/kg/day) or vehicle for four weeks. Systolic blood pressure was monitored weekly. Morphologic changes in the aortic wall were studied in picrosirius red sections. Aortic NAD(P)H activity was evaluated by luminescence. Nitrotyrosine staining was evaluated to assess peroxynitrite formation by immunohistochemistry. TGF-β and matrix metalloproteinase-9 (MMP-9) levels were determined by immunofluorescence, and p-ERK 1/2 expression by western blotting. Both β1-receptor antagonists exerted very similar antihypertensive effects (156 ± 8 mmHg and 151 ± 9 mmHg, respectively, versus 206 ± 7 mmHg in hypertensive controls; both P<0.05). However, while metoprolol had no significant effects, nebivolol significantly (all P<0.05) attenuated vascular collagen surface (237944 ± 59567, 69784 ± 17686, 183215 ± 30338 μm2, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), attenuated hypertension-induced increases in aortic NAD(P)H oxidase activity (253887 ± 13712, 143765 ± 15642, and 232465 ± 14352 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in nitrotyrosine levels (166.3 ± 2.9, 145.3 ± 1.5, 172.1 ± 7.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in TGF-β upregulation (7.2 ± 0.12, 6.5 ± 0.03, 7.0 ± 0.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups) and in MMP-9 levels (18.27 ± 0.8, 12.73 ± 0.4, 15.76 ± 1.4 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). No effects on p-ERK 1/2 expression were found with both drugs (P>0.05) (1.0 ± 0.16, 0.92 ± 0.15, 0.87 ± 0.37 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). These results show for the first time that nebivolol, but not metoprolol, attenuates prooxidant and profibrotic mechanisms involving TGF-β and MMP-9, which promote vascular remodeling in hypertension.


1957 ◽  
Vol 190 (2) ◽  
pp. 206-208 ◽  
Author(s):  
George R. Hearn ◽  
Walter W. Wainio

Young adult male Wistar rats with an average initial weight of 250 gm were exercised from 5 to 8 weeks on a training regimen consisting of swimming one-half hour daily. Pair-fed, nonswimming animals served as controls. The unit protein of the heart ventricles and gastrocnemii (mg protein/gm wet weight of organ) was in general greater for the exercised animals. Aldolase activities were determined in the heart ventricles and the gastrocnemii. The results were expressed in terms of unit activities, actual total activities and relative total activities. The exercise significantly altered the unit and relative total activities of both the heart ventricles and skeletal muscle ( P < 0.05 or < 0.01), except for the 8th week in heart, and the actual total activities of the heart ( P < 0.01), except for the 8th week.


2002 ◽  
Vol 93 (5) ◽  
pp. 1824-1832 ◽  
Author(s):  
Jatin G. Burniston ◽  
Yeelan Ng ◽  
William A. Clark ◽  
John Colyer ◽  
Lip-Bun Tan ◽  
...  

Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic β2-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 ± 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 ± 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.


1978 ◽  
Vol 89 (4) ◽  
pp. 789-795 ◽  
Author(s):  
Karl M. Pirke ◽  
Michael Geiss ◽  
Rainer Sintermann

ABSTRACT The hypothalamic-pituitary gonadal axis was studied in young adult (3 month old) and old (24 to 27 month old) male Wistar rats. Plasma testosterone decreased significantly in old animals (x̄: 262 ng/100 ml (n = 35); versus x̄: 110 ng/100 ml (n = 30)). The fall in LH was less pronounced but still significant (54.5 ng LH-RP-1/ml in young versus 39.5 ng/ml in old rats). Groups of 6 to 8 animals of both ages were castrated and implanted with silastic capsules continuously releasing testosterone. The length of the capsules was directly proportional to the plasma testosterone levels achieved (range between 63 and 350 ng/100 ml). After one week young castrated rats not substituted with testosterone showed LH values three times higher (x̄: 351 ng/ml) than old rats treated in the same way (x̄ = 126 ng/ml). LH values in the animals substituted with testosterone indicate that the sensitivity of the negative testosterone-LH feedback is greatly increased in old rats. Testosterone can be depressed to 60 ng/100 ml before an increase in LH occurs. In young rats no increase in LH was observed when testosterone values were higher than 170 ng/100 ml. In the range between 170 and 100 ng/100 ml about half of the young animals reacted with increased LH secretion, while an increase was observed in all young animals when testosterone dropped below 100 ng/100 ml.


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