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  • Author or Editor: Amanda E. Coleman x
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in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To compare the attenuation of the angiotensin I–induced blood pressure response by once-daily oral administration of various doses of angiotensin receptor blockers (irbesartan, telmisartan, and losartan), benazepril hydrochloride, or lactose monohydrate (placebo) for 8 days in clinically normal cats.

ANIMALS 6 healthy cats (approx 17 months old) with surgically implanted arterial telemetric blood pressure–measuring catheters.

PROCEDURES Cats were administered orally the placebo or each of the drug treatments (benazepril [2.5 mg/cat], irbesartan [6 and 10 mg/kg], telmisartan [0.5, 1, and 3 mg/kg], and losartan [2.5 mg/kg]) once daily for 8 days in a crossover study. Approximately 90 minutes after capsule administration on day 8, each cat was anesthetized and arterial blood pressure measurements were recorded before and after IV administration of each of 4 boluses of angiotensin I (20, 100, 500, and 1,000 ng/kg). This protocol was repeated 24 hours after benazepril treatment and telmisartan (3 mg/kg) treatment. Differences in the angiotensin I–induced change in systolic arterial blood pressure (ΔSBP) among treatments were determined.

RESULTS At 90 minutes after capsule administration, only losartan did not significantly reduce ΔSBP in response to the 3 higher angiotensin doses, compared with placebo. Among drug treatments, telmisartan (3 mg/kg dosage) attenuated ΔSBP to a significantly greater degree than benazepril and all other treatments. At 24 hours, telmisartan was more effective than benazepril (mean ± SEM ΔSBP, 15.7 ± 1.9 mm Hg vs 55.9 ± 12.42 mm Hg, respectively).

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that telmisartan administration may have advantages over benazepril administration for cats with renal or cardiovascular disease.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To identify differentially expressed microRNA in the serum and renal tissues of cats with experimentally induced chronic kidney disease (CKD).

SAMPLE

Banked renal tissues and serum from 4 cats.

PROCEDURES

Cats previously underwent 90-minute unilateral ischemia with delayed contralateral nephrectomy 3 months after ischemia. Tissues were collected from the contralateral kidney at the time of nephrectomy and from the ischemic kidney 6 months after nephrectomy (study end). Serum was collected prior to ischemia (baseline serum) and at study end (end point serum). Total RNA was isolated from tissues and serum, and microRNA sequencing was performed with differential expression analysis between the contralateral and ischemic kidney and baseline and end point serum.

RESULTS

20 microRNAs were differentially expressed between ischemic and contralateral kidneys, and 52 microRNAs were differentially expressed between end point and baseline serum. Five microRNAs were mutually differentially expressed between ischemic and contralateral kidneys and baseline and end point serum, with 4 (mir-21, mir-146, mir-199, and mir-235) having increased expression in both the ischemic kidney and end point serum and 1 (mir-382) having increased expression in the ischemic kidney and decreased expression in end point serum. Predicted target search for these microRNA revealed multiple genes previously shown to be involved in the pathogenesis of feline CKD, including hypoxia-inducible factor-1α, transforming growth factor-β, hepatocyte growth factor, fibronectin, and vascular endothelial growth factor A.

CLINICAL RELEVANCE

MicroRNAs were differentially expressed after CKD induction in this preliminary study. Regulation of renal fibrosis in feline CKD may occur through microRNA regulation of mRNAs of pro- and anti-fibrotic genes.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD).

SAMPLE

Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats.

PROCEDURES

For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys.

RESULTS

Ischemic kidneys had greater transcript levels of MMP-7, MMP-9, and transforming growth factor-β1 relative to control kidneys and of MMP-2 relative to contralateral kidneys. Transcription of TIMP-1 was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of HIF-1α did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of HIF-1α, MMP-2, MMP-7, and TIMP-1 and severity of fibrosis.

CONCLUSIONS AND CLINICAL RELEVANCE

Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To use RNA sequencing (RNAseq) to characterize renal transcriptional activities of genes associated with proinflammatory and profibrotic pathways in ischemia-induced chronic kidney disease (CKD) in cats.

SAMPLES

Banked renal tissues from 6 cats with experimentally induced CKD (renal ischemia [RI] group) and 9 healthy cats (control group).

PROCEDURES

Transcriptome analysis with RNAseq, followed by gene ontology and cluster analyses, were performed on banked tissue samples of the right kidneys (control kidneys) from cats in the control group and of both kidneys from cats in the RI group, in which unilateral (right) RI had been induced 6 months before the cats were euthanized and the ischemic kidneys (IKs) and contralateral nonischemic kidneys (CNIKs) were harvested. Results for the IKs, CNIKs, and control kidneys were compared to identify potential differentially expressed genes and overrepresented proinflammatory and profibrotic pathways.

RESULTS

Genes from the gene ontology pathways of collagen binding (eg, transforming growth factor-β1), metalloendopeptidase activity (eg, metalloproteinase [MMP]-7, MMP-9, MMP-11, MMP-13, MMP-16, MMP-23B, and MMP-28), chemokine activity, and T-cell migration were overrepresented as upregulated in tissue samples of the IKs versus control kidneys. Genes associated with the extracellular matrix (eg, TIMP-1, fibulin-1, secreted phosphoprotein-1, matrix Gla protein, and connective tissue growth factor) were upregulated in tissue samples from both the IKs and CNIKs, compared with tissues from the control kidneys.

CONCLUSIONS AND CLINICAL RELEVANCE

Unilateral ischemic injury differentially altered gene expression in both kidneys, compared with control kidneys. Fibulin-1, secreted phosphoprotein-1, and matrix Gla protein may be candidate biomarkers of active kidney injury in cats.

Full access
in American Journal of Veterinary Research