Feline hypertension
Recognition and therapy of systemic hypertension in cats is an important aspect of small animal geriatric medicine. Target organs of hypertension include the heart and vessels, the brain, the kidney, and probably most importantly, the eye. The aetiology and pathogenesis of hypertension in cats is largely unknown, but associations with hyperthyroidism, hyperaldosteronism, and renal failure have been recognized. A recent report on 69 cases seen at North Carolina State University (NCSU) for ocular disease revealed that at least 17%, and possibly as many as 50%, of cats have no identifiable cause of systemic hypertension (primary or essential hypertension). The renin-angiotensin-aldosterone system (RAAS) is probably abnormally activated in many or perhaps, most cats with systemic hypertension and certainly is activated after therapy with such drugs as loop diuretics.
Causes of hypertension in cats
Mechanisms responsible for the induction of hypertension are dependent on the associated disease process. For example, hypertension secondary to renal disease is not fully understood, but most likely is associated with the sodium retention, increased activity of the renin-angiotensin-aldosterone system, volume expansion, increased norepinephrine levels, and an increased vascular responsiveness to catecholamines.
What is known is that cardiac output is raised early in the disease course, with total peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but TPR is increased. Three theories have been proposed to explain this:
- Inability of the kidneys to excrete sodium, resulting in natriuretic factors such as Atrial Natriuretic Factor being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
- An overactive renin / angiotensin system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension.
- An overactive sympathetic nervous system, leading to increased stress responses.
Kohayashi et al. reported that 61 per cent of cats with chronic renal failure were also hypertensive. Hypertension associated with hyperthyroidism is most frequently associated with an increased stroke volume. Eighty-seven per cent of hyperthyroid cats were reported to he hypertensive (Kohayashi). In hyperthyroid cats, age, kidney disease, and vascular remodelling may also contribute to the disease. In humans, hyperthyroid patients were found to have normal to low catecholamine levels, however it has been suggested that these patients may have increased receptor sensitivity for catecholamines. Hyperaldosteronism is associated with severe hypertension attributed to sodium retention and volume expansion. Hypertension develops in 15-5O% of acromegalic humans due to volume expansion and possibly an increased tissue responsive to angiotensin II. The incidence of hypertension in acromegalic cats has not been reported. A pheochromocytoma is associated with episodic hypertension due to the release of catecholamines from a tumour of the chromatin cells in the adrenal gland. Regardless of the underlying mechanism, chronic hypertension eventually results in vascular remodelling, vascular smooth muscle hypertrophy and alterations of endothelial cell metabolism resulting in fixed hypertension. In humans, hypertension has been associated with increased relative a wave amplitude noted upon Doppler studies of mitral inflow. Littman reported that 16 of 24 hypertensive cats studied had compensatory cardiac changes.
Hypertensive changes are seen secondary to diseases such as:
3. idiopathic hypertension (unknown origin)
4. hyperaldosteronism (Primary aldosteronism - Conn's syndrome)
5. acromegaly
7. megestrol acetate use
9. corticosteroid use
10. chronic anaemia
Mechanisms of systemic hypertension
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Eye showing bleeding into the anterior chamber (in front of the lens) caused by hypertension |
Symptoms
Left untreated, hypertension inevitably damages delicate capillaries in end-artery organs ( the eyes, kidneys, heart, and brain) ( 3, 4). Hypertension may manifest as blindness, polyuria, polydipsia, cardiac irregularities, seizures, nystagmus (neurological signs), and hind limb paresis ( 3). Retinal detachment and acute blindness, the most common presenting complaints for hypertensive cats ( 2– 4), are recognized by retinal hemorrhages, tapetal hyperreflectivitiy, and vascular tortuosity on fundic examination ( 3),
Treatment
Management of hypertensive effects due to increased β-receptor sensitivity may best be achieved with specific beta-blocker therapy ( 5). The most commonly recommended drug for cats is atenelol ( 2, 3, 5, 7), which decreases the neuromuscular and cardiovascular effects of hyperthyroidism. The cat in this case might have benefited from a short course of atenolol until euthyroidism was achieved. However, β-blocker therapy might have further compromised kidney perfusion.
1) Low sodium diet - a diet moderately restricted in sodium should be offered
2) Antihypertensive agents
| Furosemide | 1 - 2 mg/kg q 12-24 hrs |
| ACE inhibitors | |
| Enalapril | 0.35 - 0.5 mg/kg q 24-48 hrs |
| Benazepril | 0.25 - 0.5 mg/kg q 24 hrs |
| Beta-blockers | |
| Atenolol | 6.25 - 12.5 mg/kg q 24hrs |
| Calcium channel blockers | |
| Diltiazem | 1.5 - 2.5 mg/kg q 8 hrs |
| Amlodipine | 0.625 mg/cat q 24 hrs |
The pathogenesis of renal-dependent hypertension is thought to be multifactorial, including decreases in ability to excrete sodium and activity of vasodilators (prostaglandins) and increases in renin secretion, norepinephrine (or response to it), and cardiac output or total peripheral resistance ( 3, 8). Increased secretion of renin (which induces increased formation of angiotensin II) may be caused by ischemic damage to kidneys and reduction of pressure, or decreased sodium chloride levels at the macula densa ( 2, 8). An overactive renin-angiotensin-aldosterone system causes hypertension by a combination of volume excess and vasoconstrictor mechanisms, and ongoing hypertension may accelerate renal lesions ( 8). Activation of the renin-angiotensin-aldosterone-system may stimulate production of endothelin, a potent vasoconstrictor found in vascular endothelial cells and vascular smooth muscle ( 2). Future therapies may be directed at countering the ischemia produced by this vasoconstriction.
Hypertension in cats may not always be associated with renin-dependent mechanisms ( 8, 9), explaining the apparent failure of treatments aimed at inhibiting angiotensin II production ( 7– 9). Primary hypertension in felines may be responsible for progression to renal failure, rather than the reverse ( 4). Angiotensin-converting enzyme inhibitors, including enalapril, decrease blood pressure and increase renal perfusion and glomerular filtration rate ( 4, 9).
Amlodipine is a calcium channel blocker that relaxes vascular smooth muscle without the myocardial depressive effect of many calcium channel antagonists ( 4). In cats, amlodipine is long acting (24 h), safe, and effective, and may be renoprotective ( 9, 10). It is reported to be the most effective therapy for hypertensive cats ( 2, 6, 7, 9). It was not used in this case because blood pressure could not be monitored accurately. There have been recent reports that calcium channel blockers cause renal injury and proteinuria in humans and in diabetic dogs ( 10). Amlodipine and angiotensin-converting-enzyme inhibitors may be used safely and effectively in combination ( 7), offering vasodilation of both afferent and efferent arterioles.
