A comparative study of morphological changes in spontaneously hypertensive rats and normotensive Wistar Kyoto rats treated with an angiotensin-converting enzyme inhibitor or a calcium-channel blocker

Saleh, Farid H.

doi:10.1002/1096-9896(2000)9999:9999<::aid-path796>3.0.co;2-f

Cited by 18 publications

(5 citation statements)

References 25 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…hypertension with or without a reduction in blood pressure. [27][28][29] In monkeys, local Ang II is mainly generated via ACE-and chymase-dependent pathways. 30,31 In the present study, intimal ACE and Ang II staining were both increased with age, suggesting the presence of an age-associated increase in Ang II production through an ACE-dependent pathway and signaling.…”

Section: Discussionmentioning

confidence: 99%

Aging Increases Aortic MMP-2 Activity and Angiotensin II in Nonhuman Primates

et al. 2003

View full text Add to dashboard Cite

Abstract-To seek evidence that the nonhuman primate arterial wall, as it ages in the absence of atherosclerosis, exhibits alterations in pathways that are involved in the pathogenesis of experimental atherosclerosis, we assessed aortic matrix metalloproteinase-2 (MMP-2) and its regulators, ie, membrane type-1 of matrix metalloproteinase (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and the expression of angiotensin II (Ang II), angiotensinconverting enzyme (ACE), and chymase in young (6.4Ϯ0.7 years) and old (20.0Ϯ1.9 years) male monkeys. With advancing age, (1) the intimal thickness increased 3-fold and contained numerous vascular smooth muscle cells and matrix, but no inflammatory cells; (2) the intimal MMP-2 antibody-staining fraction increased by 80% (PϽ0.01); (3) in situ zymography showed that MMP-2 activity, mainly confined to the intima, increased 3-fold (PϽ0.01); (4) the MT1-MMP antibody-staining fraction increased by 150% (PϽ0.001), but the TIMP-2 antibody-staining fraction did not significantly change; (5) steady levels of the mRNA-staining fraction (via in situ hybridization) for MMP-2 increased 7-fold, for MT1-MMP increased 9-fold, and for TIMP-2 increased 2-fold (all PϽ0.001); and (6) intimal Ang II and ACE immunofluorescence were increased 5-fold and 5.6-fold, respectively, and colocalized with MMP-2. Thus, age-associated arterial remodeling and the development and progression of experimental atherosclerosis in young animals share common mechanisms, ie, MMP-2 activation and increased Ang II signaling. This might explain, in part, the dramatically exaggerated prevalence and severity of vascular diseases with aging.

show abstract

Section: Discussionmentioning

confidence: 99%

Aging Increases Aortic MMP-2 Activity and Angiotensin II in Nonhuman Primates

et al. 2003

View full text Add to dashboard Cite

show abstract

“…We could not find direct experimental data regarding TAL volume in SHR. However, kidney weights in SHR, when normalized for body weight, have been found to be similar to (48), or larger than (40), kidney weights in WKY control rats, which suggests similar or larger TAL volumes between strains, if TAL volume scales with kidney weight. The available data concerning nephron flows in SHR are mixed.…”

Section: Applicable Findings From the Experimental Recordmentioning

confidence: 93%

Multistability in tubuloglomerular feedback and spectral complexity in spontaneously hypertensive rats

Layton¹,

Moore²,

Layton³

2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Single-nephron proximal tubule pressure in spontaneously hypertensive rats (SHR) can exhibit highly irregular oscillations similar to deterministic chaos. We used a mathematical model of tubuloglomerular feedback (TGF) to investigate potential sources of the irregular oscillations and the corresponding complex power spectra in SHR. A bifurcation analysis of the TGF model equations, for nonzero thick ascending limb (TAL) NaCl permeability, was performed by finding roots of the characteristic equation, and numerical simulations of model solutions were conducted to assist in the interpretation of the analysis. These techniques revealed four parameter regions, consistent with TGF gain and delays in SHR, where multiple stable model solutions are possible: 1) a region having one stable, time-independent steady-state solution; 2) a region having one stable oscillatory solution only, of frequency f1; 3) a region having one stable oscillatory solution only, of frequency f2, which is approximately equal to 2f1; and 4) a region having two possible stable oscillatory solutions, of frequencies f1 and f2. In addition, we conducted simulations in which TAL volume was assumed to vary as a function of time and simulations in which two or three nephrons were assumed to have coupled TGF systems. Four potential sources of spectral complexity in SHR were identified: 1) bifurcations that permit switching between different stable oscillatory modes, leading to multiple spectral peaks and their respective harmonic peaks; 2) sustained lability in delay parameters, leading to broadening of peaks and of their harmonics; 3) episodic, but abrupt, lability in delay parameters, leading to multiple peaks and their harmonics; and 4) coupling of small numbers of nephrons, leading to multiple peaks and their harmonics. We conclude that the TGF system in SHR may exhibit multistability and that the complex power spectra of the irregular TGF fluctuations in this strain may be explained by switching between multiple dynamic modes, temporal variation in TGF parameters, and nephron coupling.

show abstract

“…Decreased LV hypertrophy, but did not enhance vascularization in the adult SHRs Saleh and Jurjus [63] Enalapril 150 mg/l 21 weeks Prevented LV, aortic arch and kidney hypertrophies and the thickening of the aortic media layer seen in untreated SHRs Gasparo et al [64] Enalapril and 1 and 5 4 weeks Improved endothelial function and tissue injury in SHRs valsartan receiving L-NAME Zorzi et al [44] Enalapril 15 [40]. Table 1 compares the different studies using ACEIs in recent years to treat LV hypertrophy and its consequences.…”

Section: Authorsmentioning

confidence: 82%

Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats

et al. 2004

View full text Add to dashboard Cite

Stereological structural alterations of the heart and kidney were studied in four groups (n=5) of spontaneously hypertensive rats (SHRs) treated for 30 days: (i) control, (ii) NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthesis inhibitor] alone, (iii) enalapril alone and (iv) L-NAME plus enalapril. Blood pressure (BP) was elevated significantly in NO-deficient SHRs (rats receiving L-NAME) or significantly lower in enalapril-treated SHRs. Co-administration of L-NAME and enalapril caused a 20% decrease in BP compared with untreated SHRs. NO-deficient SHRs had a decrease in body mass, but this loss of body mass was prevented efficiently in the enalapril-treated group. Enalapril treatment decreased the left ventricular (LV) mass index in SHRs, even in animals with NO synthesis blocked. NO deficiency in SHRs caused a larger decrease in the number of LV cardiomyocyte nuclei, which had a negative correlation with both LV mass index and BP. The volume-weighted glomerular volume (VWGV) separated the SHRs into two groupings: (i) control and NO-deficient SHRs, and (ii) enalapril- and L-NAME plus enalapril-treated SHRs. There was a significant difference between these two groupings, with VWGV being more than 15% smaller in the latter compared with the former grouping. The present findings reinforce the evidence that enalapril efficiently treats genetic hypertension, and demonstrate that this effect is observed even when NO synthesis is inhibited. Enalapril administration also decreases cardiac and renal structural damage caused by genetic hypertension, as well as by the interaction between genetic hypertension and NO deficiency.

show abstract

A comparative study of morphological changes in spontaneously hypertensive rats and normotensive Wistar Kyoto rats treated with an angiotensin-converting enzyme inhibitor or a calcium-channel blocker

Cited by 18 publications

References 25 publications

Aging Increases Aortic MMP-2 Activity and Angiotensin II in Nonhuman Primates

Aging Increases Aortic MMP-2 Activity and Angiotensin II in Nonhuman Primates

Multistability in tubuloglomerular feedback and spectral complexity in spontaneously hypertensive rats

Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats

Contact Info

Product

Resources

About