Systemic hypertension is defined as a sustained increase in arterial pressure. Hypertension is diagnosed when systolic pressure is > 160 mm Hg. Contrary to widespread belief, diastolic blood pressure does not reflect vascular function better than systolic pressure and its measurement does not provide any additional information. Vascular function cannot be adequately described in the time domain (systolic versus diastolic). It is ideally evaluated in the frequency domain by evaluating the impedance spectrum. However this is not clinically feasible. Severe systemic hypertension can create end-organ damage clinically-manifested as blindness (retinal hemorrhages, retinal detachments), seizures, heart disease, dyspnea, and epistaxis. Systemic hypertension is a major risk factor for the progression of kidney disease in people, dogs, and likely in cats.

Arterial pressure is clinically measured using Doppler or oscillometric methods, or by direct arterial puncture. The most common causes of hypertension in cats are renal disease and hyperthyroidism. Diabetic cats also can be hypertensive. Clinical signs of systemic hypertension are vague and may include ocular (e.g., retinal detachment, retinal bleeding), neurologic (e.g., cerebral signs, head tremor), and cardiovascular (e.g., heart murmur, gallop rhythm, left ventricular hypertrophy) abnormalities. Non-specific signs (e.g., epistaxis) may also occur. It is important to remember that most hypertensive cats have minimal or no clinical signs even when severely hypertensive. Systemic hypertension is associated with small vessel disease leading to end-organ damage. Hypertensive patients may develop cardiac, renal, ocular and neurologic problems. Hypertension is not only a cause of renal disease, but can also favor progression of renal failure due to associated intraglomerular hypertension. Intraglomerular hypertension also favors proteinuria, another risk factor for progression of renal disease.

Therapy of hypertension is directed at deceasing cardiac output (e.g., beta-adrenoceptor blockers) or peripheral vascular resistance (e.g., vasodilators). Low-sodium diets and diuretics decrease circulating volume and can be used as adjuvant therapy, but are not likely to be effective as sole measures. Proteinuria is an earlier indicator of glomerular damage and is independently associated with progression of renal failure in cats. Thus, proteinuria must always be evaluated and controlled in hypertensive patients.

Drugs Used to Treat Hypertension

Beta-adrenoceptor blockers (e.g., atenolol 6,25 mg, q12-24h) decrease heart rate and cardiac contractility. They are used primarily in hyperthyroid cats, particularly if they are also tachycardic. Beta-adrenoceptor blockers are not very effective in other causes of hypertension, but may be considered as adjuvant therapy in refractory hypertension.

Amlodipine is a long-acting dihydropyridine calcium antagonist drug that is very effective in controlling hypertension in cats. Amlodipine is usually successful in lowering blood pressure as a single agent. If clinically-indicated, amlodipine may be combined with either an ACE inhibitor or a beta-adrenoceptor-blocker. Amlodipine is administered once daily based on the long half-life (e.g., 30 hours in the dog, 35 hours in humans). The half-life of amlodipine in cats is not known, but its clinical effects may last over 30 hours. The typical dose is 0,625 mg/cat once daily, although cats > 5 kg may require 1,25 mg/day. Caution should be exercised when using amlodipine as sole drug in patients with renal failure because it selective dilates the afferent artery in the glomerulus and may increase intraglomerular pressure (Hayashi et al, 1996, 2003).

ACE inhibitors (enalapril 0,5 mg/kg q12-24h and benazepril 0,25-0,5 mg/kg q12-24h) also decrease peripheral vascular resistance, but the effect is less pronounced than that of amlodipine. However, ACE inhibitors have a more pronounced nephroprotective effect. In addition, they prevent vascular remodeling, and decrease proteinuria and renal excretion of angiotensin II. ACE inhibitors should be used in hypertensive patients with renal failure or proteinuria.

Hydralazine (2,5 mg q12h) is a potent direct-acting arterial dilator with a rapid onset of action (1 hour, with maximum effects in 3 to 5 hours). It is used for acute control of hypertension (e.g., when neurologic or ocular signs are present) in hospitalized patients with serial monitoring of blood pressure and creatinine, or in refractory hypertension.

Sodium nitroprusside (1,0-5,0 µg/kg/min as a continuous infusion) is a nitrate given by constant rate infusion, and has primarily arterial dilating properties. It is the drug of choice for the hypertensive crisis. It is best used in a referral or emergency hospital where constant arterial blood pressure monitoring can occur.

Management

All patients with systolic pressure > 160 mm Hg and clinical signs of hypertension or a disease known to cause hypertension should be treated. Asymptomatic patients without an identifiable disease associated with hypertension should be retested in one week to assure that they are really hypertensive. Patients with systolic pressure > 220 mm Hg are in hypertensive crisis and should be treated aggressively in-hospital. Periodic measurements of blood pressure are necessary to evaluate the efficacy of anti-hypertensive therapy. In stable patients with systolic pressure < 220 mmHg, blood pressured can be evaluated within 7 days. In our hospital, we obtain a new blood pressure and a creatinine concentration every 7 to 10 days until blood pressure is below 160 mm Hg. Patients with glomerular disease or diabetes mellitus may require a more aggressive end-point (systolic pressure < 145 mmHg) to provide further nephroprotection. Once hypertension is controlled, patients should be rechecked every 3-4 months. During a hypertensive crisis, arterial pressure should be constantly monitored until control is achieved.

How I Treat--Cats

Stable cat with renal failure or proteinuria: In these patients nephroprotection is almost as important as reduction of arterial pressure. Unfortunately, ACE inhibitors are not effective in controlling pressure cats with renal failure. Thus a combination of an ACE inhibitor and amlodipine is ideal in this population. Amlodipine controls blood pressure, whereas ACE inhibitors provides nephroprotection. ACE inhibitors also prevent worsening of proteinuria, a known factor associated with progression of renal failure in cats. Many veterinarians prefer to use amlodipine as the sole drug in this population of cats. However, care should be taken to assure that an adequate control of blood pressure is obtained. Amlodipine selectively dilate the afferent artery of the glomerulus. If blood pressure is not normalized, the glomerulus may be exposed to the high systemic pressure, worsening glomerular hypertension.

Stable cat with diabetes mellitus: These cats have a high risk for kidney damage and are managed like patients with hypertension and renal disease.

Stable cat with hyperthyroidism: Sympathetic activation is one of the mechanisms associated with hypertension in hyperthyroidism. Thus, beta-adrenoceptor blockers are the drugs traditionally used in these cats. Control of hyperthyroidism should also be attempted, despite the fact that some cats will remain hypertensive even after correction of the hyperthyroidism.

Stable cat with no identifiable underlying cause for hypertension: In these patients, all drugs that have the potential to increase blood pressure should be discontinued, if possible. Uncommon causes of hypertension (e.g., primary hyperaldosteronism, pheochromocytoma) should be pursued and ruled-out. Hypertension in patients with pheochromocytoma is best controlled with an association of phenoxybenzamine and propranolol. If a disease responsible for the hypertension cannot be found, therapy can be started with amlodipine and, if needed, an ACE inhibitor.

References

1.  Brown S, Atkins C, Bagley R, et al. Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med. 2007; 21: 542-558

2.  Elliott J, Barber PJ, Syme HM, et al. Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases. J Small Anim Pract. 2001; 42:122-129.

3.  Hayashi K, Nagahama T, Oka K, et al. Disparate effects of calcium antagonists on renal microcirculation. Hypertens Res 1996;19:31-36

4.  Hayashi K, Ozawa Y, Fujiwara K, et al. Role of actions of calcium antagonists on efferent arterioles--with special references to glomerular hypertension. Am J Nephrol 2003;23:229-244

5.  Henik R, Dolson M, Wenholz L. How to obtain a blood pressure measurement. Clin Tech Small Anim Pract. 2005; 20:144-150

6.  Stiles J, Polzin DJ, Bistner SI. The prevalence of retinopathy in cats with systemic hypertension and chronic renal failure or hyperthyroidism. J Am Anim Hosp Assoc. 1994; 30:564-572

7.  Syme H, Barber P, Markwell P, Elliott J. Prevalence of systolic hypertension in cats with chronic renal failure at initial evaluation. J Am Vet Med Assoc. 2002; 220:1799-1803.