Development of Hypertension and Effects of Benazepril Hydrochloride in a Canine Remnant Kidney Model of Chronic Renal Failure

Abstract

ABSTRACT. In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre-and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (p<0.05), creatinine clearance was decreased (p<0.05), and blood pressure was increased significantly (p<0.05). Simultaneously, plasma renin activity, angiotensin I and II, and aldosterone were elevated significantly (p<0.05) compared with the values obtained from 11 healthy dogs with intact renal function. The dogs with induced renal failure and hypertension were administered an angiotensin-converting enzyme inhibitor, benazepril hydrochloride, once daily for 2 weeks at 2 mg/kg body weight, and changes in blood pressure and the renin-angiotensin-aldosterone (RAA) system were determined. During the administration of benazepril hydrochloride, blood pressure, angiotensin II and aldosterone decreased significantly (p<0.05) and, upon discontinuation of administration, increased to the pre-administration levels (p<0.05). Plasma renin activity and angiotensin I showed no significant changes throughout the administration study. These results provide experimental evidence that hypertension develops in dogs with chronic renal failure through mechanisms involving the RAA system and demonstrate that benazepril hydrochloride improves renal hypertension in dogs. KEY WORDS: angiotensin-converting enzyme inhibitor, benazepril, canine, renal ablation, renal hypertension.J. Vet. Med. Sci. 70 (5): [455][456][457][458][459][460] 2008 Hypertension is classified into essential and secondary hypertension and, in humans, essential hypertension accounts for 80 to 90% of hypertension patients [24]. In contrast, essential hypertension is relatively rare in veterinary practice [7,33]. Underlying reasons are that hypertension per se has no characteristic symptoms and blood pressure is not routinely determined in veterinary practice. Therefore, it is important to diagnose diseases that would lead to secondary hypertension and to identify the risk of developing secondary hypertension. Causes of secondary hypertension include renoparenchymal diseases, renovascular diseases, diabetes, Cushing syndrome, primary hyperaldosteronism, pheochromocytoma and hypothyroidism and, of those, renoparenchymal disease-associated hypertension is most common in humans [24]. The mechanism of renal hypertension is thought to involve renal insufficiency-associated body fluid retention, increases in cardiac output and peripheral vessel resistance, activation of the renin-angiotensin-aldosterone (RAA) system and suppression of the kallikrein-kinin-prostaglandin system [2,3,17].A link between chronic renal failure and hypertension has been suggested in dogs and cats [1,6,12,13,22,26,27,29,30,34,[36][37][38]. Activation of the RAA system and development of hypertension in association with renal failure have been reported in cats [20,30,41]. ...

Impact of Chronic Kidney Disease on Myocardial Blood Flow Regulation in Dogs

“…Strengths of this animal model include the ability to induce progressive renal insufficiency with only transient increases in systolic arterial pressure. Systemic arterial hypertension was not manifest in this study and others [13,35,36] despite the considerable loss of functioning nephrons and renal mass [37]. Systolic arterial pressure was transiently increased in CKD dogs but stabilized near baseline levels by the end of the 5-week period.…”

Influence of feeding schedules on the chronobiology of renin activity, urinary electrolytes and blood pressure in dogs

“…These variations are consistent with our previous findings, and support earlier observations from Piccione et al (2005). The levels of SBP and DBP reported herein are similar to those from earlier experiments in dogs (Mishina & Watanabe, 2008;Miyazaki et al, 2002;Mochel et al, 2013).…”

Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

“…Similar to temocapril, benazepril is also an ACEI that causes long-lasting and preferential biliary excretion. Significant antihypertensive effects of benazepril in dogs with CKD involving systemic hypertension have already been demonstrated experimentally and clinically in previous reports [9,13]. Although the findings from the present case indicated that temocapril is an effective antihypertensive agent, its superiority to other ACEIs has not yet been demonstrated.…”

“…In human medicine, the term hypertensive nephrosclerosis (HN) was used to describe the renal injury caused by essential hypertension [9]. Although human HN is usually diagnosed solely on clinical grounds, importance of the pathological analysis of renal biopsy results has been pointed out recently [10,11].…”