The University of Georgia College of Veterinary Medicine

Georgia Veterinary Scholar Program

Georgia Veterinary Scholar	Faculty Mentor

Carrie Jurney University of Georgia Class of 2005	Dr. Scott Brown

Efficacy and Safety of the Calcium Channel Blocker Amlodipine Besylate in Cats with Renal Insufficiency

Calcium channel blockers (CCB) have been used to treat systemic hypertension in both people and cats. The vasodilatory effects of certain CCBs make them an intriguing candidate for control of secondary hypertension in feline renal patients. Clinical trials with the dihydropyridine-type CCB, amlodipine besylate, suggest they will lower blood pressure in hypertensive cats; however, there has been little data available to address the safety of these drugs, especially in cats with co-existing renal disease. Some studies indicate that the use of CCBs may increase proteinuria, glomerulosclerosis and tubulointerstitial inflammation.

Our hypothesis is that the CCB, amlodipine, would lower systemic blood pressure in cats with renal insufficiency and this antihypertensive effect would activate the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) and lead to a pro-inflammatory condition within the kidney. To test this hypothesis, 20 cats were placed on alternating periods of treatment with either placebo or 0.25 mg/kg of amlodipine given orally once daily. The study group consisted of a control group (n=7; Control group) and a group of cats with reduce renal function (n=13; Azotemic Group). Renin, aldosterone, and catecholamines were measured in each treatment period to assess the activity of the RAAS system. Creatinine and electrolytes were also measured to evaluate renal function. Urine was assayed for three pro-inflammatory molecules: Monocyte Chemotactic protein 1, Prostaglandin E2 and Transforming Growth Factor Beta-1. At the end of the treatment period, a renal biopsy was obtained for histology and immunohistochemistry.

Blood pressure was significantly altered with amlodipine administration in both study groups (p=.01). The Azotemic group shows a significant increase (p = 0.0529) in TGF-B1 with the administration of Amlodipine. Controls also show an increase in TGF-B1, but it was not significant (p = 0.25). PGE-2 increases significantly (p=0.0021) in the control group with amlodipine administration. Conversely, the Azotemic group shows a significant decrease (p= 0.0005) in levels of PGE-2 while on amlodipine. Both groups show an increase in both renin and catecholamines while on amlodipine, however these increases were not significant. We conclude that while amlodipine is efficacious for treating cats with hypertension, it may activate the RAAS and SNS and therefore lead to detrimental inflammatory processes in the kidney.