Effect of Chronic Hypertension on Renal Function in Dogs
World Small Animal Veterinary Association World Congress Proceedings, 2003
Kenneth C. Bovee, DVM, M Med Sc
Emeritus Professor of Medicine, University of Pennsylvania
Philadelphia, PA, USA

INTRODUCTION

The measurement of blood pressure is seldom done in clinical dogs because the procedure is difficult and time consuming, there is a lack of standards, and the significance of elevated pressure is poorly understood. Hypertension has been extensively studies in rats and humans but little investigation has been done in dogs even though the dog has been used as an animal model for humans. Hypertension has been shown to produce cardiovascular and renal dysfunction but this has not been studied in dogs. With the availability of a genetic colony of hypertensive dogs we have studied the possible pathophysiology of hypertension.

PHYSIOLOGY OF HYPERTENSION

The regulation of blood pressure is normally maintained by a number of neural, hormonal, cardiovascular and renal mechanisms. When one or more of these mechanisms malfunctions, the result is abnormal variations of either high or low blood pressure. Hypertension is defined as the continual high pressure state that may lead to injury of the vasculature or end organs. Hypertension may be classified as being secondary to diseases that cause abnormal regulation of maintenance factors, or of undetermined origin known as essential hypertension.

In rats and humans the more common causes of secondary hypertension include: a hyperactive renin-angiotensin system, salt sensitivity, hyperaldosteronism, excessive cortisol and ACTH, catecholamine hyperactivity, hyperinsulinemia of diabetes mellitus, thyroid disease, obesity, and renal failure. Essential hypertension is due to complex abnormalities of the renal, hormonal and neural mechanisms that control blood pressure. Many of the above have not been reported to cause hypertension in dogs, but since hypertension is seldom measured or suspected at necropsy many questions remain open.

During the past 20 years a number of experimental studies have addressed the mechanisms that may cause hypertension in dogs. The results indicate that hypertension in dogs does not appear to be influenced by salt sensitivity or salt loading, excessive cortisol and ACTH, hyperinsulinemia, reduced renal mass or chronic renal failure. Evidence about obesity is equivocal and thyroid disease has not been studied. The factors that do cause hypertension in dogs are hyperaldosteronism, hyperactive renin-angiotensin system, catecholamine hyperactivity and DOCA with salt loading.

CLASSICAL PATHOLOGY OF HYPERTENSION

In rats and man it is well known that sustained hypertension is associated with salt retention, increased sodium and calcium in endothelial cells, enhanced vascular tone, altered endothelial architecture, smooth muscle cell proliferation and fibrosis of arterioles which leads to reduced blood flow. These changes occur in many tissues but are most prominent in the heart, kidney and brain leading to reduced function. In humans the most prominent hypertension induced renal diseases are diabetes mellitus, nephrosclerosis and renovascular hypertension. Treatment to control these diseases is renal sparing. In dogs these diseases either do not cause hypertension or are rare. Since this classic pathology has not been documented in dogs it may not be relevant.

MEASUREMENT OF BLOOD PRESSURE IN DOGS

Several methods of measurement including direct, indirect, short term, and continuous have been used in laboratory settings and clinics. We have compared several of these and found that the most reliable and accurate is the use of a continuous direct measurement using a telemetry system. Other methods have major limitations and often overestimate pressure. The telemetry system requires an implanted arterial catheter and sophisticated electronic and computer systems and is not practical for clinical use. Using a continuous 24 hour recording it represents the gold standard and method of choice to study the significance of hypertension in dogs. The most consistent measure of blood pressure is provided by mean arterial pressure, MAP. Normal values using this method are: systolic 144, diastolic 71, mean 95+3 mm Hg, and heart rate 83/ minute.

HEREDITARY ESSENTIAL HYPERTENSIVE DOGS

We have produced a colony of hypertensive dogs by breeding a pair of unrelated dogs with essential hypertension. Over 20 years of line breeding we have produced 120 offspring with varying degrees of hypertension and normotensive dogs. The colony, named PHD, is characterized as having: high and borderline hypertension, normal kidney function, normal plasma chemistry and electrolytes, normal renin, aldosterone and ADH, sodium insensitivity, pattern of labile blood pressure, normal cardiac function, normal histopathology, increased plasma NE, and increased catecholamine spillover. Despite these abnormal findings this colony is classed as being essential hypertension. Over the period of breeding these dogs we have monitored kidney function in young and aging animals.

RENAL FUNCTION WITH AGING

The objective of this study was to determine the influence of chronic hypertension of several years duration on renal function. Blood pressure was recorded using a continuous telemetry system for several days at intervals of 6 to12 months over years. Renal function was measured annually using standard clearance methods and finally histopathology was performed on all older dogs to detect possible changes. The study included l9 high and borderline PHD and 17 normotensive PHD. Blood pressure in the hypertensive group was > 120 MAP and in the borderline hypertensive group was 110-120 MAP. Glomerular filtration rate was measured with the clearance of inulin and creatinine and renal plasma flow was estimated by the clearance of para-aminohippurate. Routine hematology and chemistry were recorded annually. Urinalysis and urinary protein/creatinine ratio was measured annually.

The results of GFR measures between dogs in 3 age groups, 1-3, 4-6, and 7-13 years did not show a pattern of decrease with time. Renal plasma flow was not changed over time, the only significant difference being a lower RPF in the normotensive dogs in the oldest age group. Values for both GFR and RPF remained normal compared to normal unrelated dogs. Plasma chemistry, hematology and urinalysis remained normal. Urinary protein/creatinine ratio was less than 1.0 in both groups.

All dogs were euthanized at 7-13 years of age and a detailed histopathology analysis was performed with special attention and multiple sectioning of the vasculature of the heart, kidney, renal artery, abdominal aorta, tongue and brain. The most consistent changes were mild endocardiosis, mild nodular fibrosis of the left AV valve leaflets, mild intimal fibrosis of the renal artery, and mild lymphoplasmatic tubulointerstitial nephritis. These findings were the same in both groups of dogs and considered normal for older dogs.

In conclusion, results of the renal function studies and histopathology found no difference between hypertensive and normotensive dogs from this linebred colony studied for many years. Histopathology also found no confounding or contributing factors to confuse the results. Renal function remained normal in hypertensive dogs. These findings suggest that the mechanisms associated with the pathophysiology of hypertension in other species do not apply to dogs, at least in this unique model of essential hypertension.

References

1.  Bovee, KC, Littman MP et al: Essential hereditary hypertension in dogs: a new animal model. J Hypertension 4(5);Sl72-Sl73, l986

2.  Papanek, PE, Bovee KC, Skelton MM, AW Cowley: Chronic pressure-natriuresis relationship in dogs with inherited essential hypertension. AJH 6;960-967, l993

3.  Bovee, KC, Buranachol C and Watanabe T, Comparison of direct arterial blood pressure between repeated short interval measures and continuous 24 hour recording in genetically hypertensive dogs. A Jour Vet Int Med 7; no.2, l993

Speaker Information
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Kenneth C. Bovee, DVM, M Med Sc
Emeritus Professor of Medicine, University of Pennsylvania
Philadelphia, PA, USA


MAIN : Urology : Hypertension and Renal Function
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