Chapter 236. Systemic Hypertension

Question 1

What is the normal blood pressure of dogs?

Answer 1

Range of 111-162 mmHg SBP

Question 2

What is the normal blood pressure in cats?

Answer 2

SBP 131-154 mm Hg

Question 3

What are the types of systemic hypertension?

Answer 3

• Secondary hypertension
• Idiopathic hypertension
• Situational hypertension

Question 4

What the aetiology of secondary hypertension?

Answer 4

1. Renal disease (Most common)
2. Hyperadrenocorticism
3. Adrenal tumours/hyperplasia
4. Hyperthyroidism
5. Diabetes Mellitus
6. Cardiovascular disease

Question 5

Describe the pathophysiologic mechanism of systemic hypertension in renal disease.

Answer 5

The pathophysiologic mechanism is multifactorial. Impaired renal function leads to:
1. Activation of systemic and intrarenal RAAS, resulting in increased angiotensin II (ATII) and aldosterone (ALDO), which promote sodium retention, vascular smooth muscle constriction which increases SVR results in and increased preload and subsequently blood pressure as MAP = CO x SVR.
2. Sympathetic nervous system stimulation activation results in an increased HR, SV and vasoconstriction. Increase HR and SV results in increased CO (CO = SV x HR), this ultimately leads to an increase ion MAP (MAP = CO x SVR).
3. Endothelial dysfunction and vascular changes contribute via:
↓ Nitric oxide (NO) to reduced vasodilation and ↑ endothelin and thromboxane (TXA) which are potential vasoconstrictors = ultimately results in, increasing vascular resistance (SVR).
Excessive angiotensin II (ATII) and aldosterone (ALDO) are directly nephrotoxic and likely contribute to fibrotic remodeling of glomeruli. ATII is also locally produced in the renal parenchyma. This intrarenal RAAS promotes glomerular hypertension, worsens proteinuria, and leads to oxidative damage and renal fibrosis.
Proteinuria worsens kidney damage:
* Drives inflammation, glomerulosclerosis, and fibrosis.
* Independently associated with poor outcomes in feline CKD.
SH itself exacerbates renal injury: Increases intraglomerular pressure and promotes proteinuria, creating a vicious cycle.
Acute kidney injury (AKI) is also associated with SH (prevalence ~59% in cats), especially when complicated by:
* Volume overload from fluid therapy.
* Use of erythropoiesis-stimulating agents.

Question 6

Describe the pathophysiology of systemic hypertension in hyperadrenocorticism.

Answer 6

1. Proposed mechanisms (mainly extrapolated from human studies):
   o Increased mineralocorticoid activity may occur along with the cortisol excess. Cortisol may stimulate renin substrate synthesis and increase the expression of angiotensin II receptors.
   o Glucocorticoid-induced suppression of vasodilators (e.g., nitric oxide). Glucocorticoids may raise CO, total peripheral resistance, and renal blood flow, contributing to SH.
2. Glomerular damage and proteinuria may also play a role.

Question 7

What is the pathophysiology of adrenal tumours and systemic hypertension?

Answer 7

Pheochromocytomas reported in dogs and cats can result in increased catecholamine secretion and excessive alpha- and beta-adrenergic stimulation. This may cause sustained or paroxysmal SH.

Question 8

What is the pathophysiology of systemic hypertension in hyperthyroidism?

Answer 8

Pathogenesis is poorly understood, excessive thyroxine causes substantial reduction in systemic vascular resistance (SVR), decreased diastolic BP and reflexive increase in CO in people. This triggers activation of RAAS, contributing to increased BP. Thyroid hormones also increase catecholamine sensitivity, increasing cardiac inotropy and chronotropy.

Question 9

Describe the pathophysiology of systemic hypertension in diabetes mellitus?

Answer 9

Pathophysiology is not well understood but is thought that loss of insulin may lead to decreased natural vasodilatory effect (NO generation), increased Na+ and water retention, increased intracellular Ca2+ leading to increased vascular smooth muscle contractility, proliferation of vascular smooth muscle, and sympathetic nervous system stimulation. Result in and increase in HR, therefore and increase CO in which MAP = CO x SVR. The increase in SVR ultimately results in and increase in MAP as well.

Question 10

Define situational hypertension.

Answer 10

Transient increase in systemic BP in the hospital setting

Question 11

Describe the pathophysiology of situational hypertension

Answer 11

Considered to be a result of transient sympathetic nervous system activation

Question 12

What is the prevalence of idiopathic hypertension in dogs and cats?

Answer 12

• True idiopathic hypertension is rare in dogs
• In cats, reported prevalence between 13-24%
• In cats the prevalence is thought to be actually much lower due to overlooked early CKD as when compared to a population of normotensive non-azotemic geriatric cats, cats with SH had a significantly higher plasma creatinine concentration (but were still non-azotemic) and lower urine specific gravity.

Question 13

What is target organ damage? Which organ are most commonly affected?

Answer 13

The structural or functional impairment of vital organs. Most common affected organs include the eyes, brain, heart and kidneys.

Question 14

What is the minimum clinical blood pressure goal to reduce the risk of target organ development?

Answer 14

The consensus statement of systemic hypertension suggests an ideal SBP target of < 140mmHg. An SBP ≤160 mm Hg should be the minimum clinical goal to reduce risk of TOD.

Question 15

What is the most common site of target organ damage?

Answer 15

The eye.

Question 16

Describe the pathophysiology of the development of ocular change in systemic hypertension.

Answer 16

Elevated BP overwhelms retinal autoregulation, causing choroidopathy/retinopathy, barrier breakdown, and reduced perfusion. Sustained SH can lead to vasoconstriction, ischemia, increased permeability, and hemorrhage.

Question 17

What are the common ocular lesions caused by systemic hypertension?

Answer 17

1. Partial to complete retinal detachment and Retinal perivascular edema
2. Hemorrhage (pre- and intra-retinal haemorhage)
3. Multifocal edema
4. Retinal vessel tortuosity
5. Papilledema
6. Optic nerve atrophy
7. Vitreous hemorrhage: Anterior chamber involvement, like hyphema or iris hemorrhage, is less frequent but more common in dogs.
8. Chronically can cause degenerative retinal changes, such as pigment alterations and vascular attenuation.

Question 18

What are the vascular manifestations of systemic hypertension?

Answer 18

Systemic hypertension causes vasculopathy marked by endothelial dysfunction and arterial remodeling (e.g., arteriosclerosis, smooth muscle hypertrophy, increased collagen), leading to reduced vascular elasticity and impaired dilation.

Question 19

What are the cardiac manifestations of systemic hypertension?

Answer 19

Structural Changes:
* Increased wall tension (pressure overload) results in myocardial mechanoreceptor activation, leading to increased synthesis of myocardial proteins and associated tissue, leading to left ventricular hypertrophy (LVH).
* Aortic dilation
* Myocardial fibrosis
Functional Changes:
* Diastolic dysfunction is common and may occur before fibrosis or hypertrophy.
Other Cardiac Effects:
* Left atrial enlargement and congestive heart failure are uncommon i- reported in 12% of dogs and 28% of cats.
* Reduced coronary reserve may occur, though direct coronary vasculature remodeling is rare.
* Arrhythmias are possible due to RAAS activation and catecholamines.

Question 20

What are the renal manifestation of systemic hypertension?

Answer 20

Hypertensive nephrosclerosis involves vascular changes (intimal thickening, afferent arteriole hyalinosis, glomerular capillary occlusion, elastic fiber breakdown) and glomerular changes (collagen replacement, extracellular matrix deposition, capsular adhesions/scarring), leading to altered renal blood flow and glomerulosclerosis. Vascular narrowing can reduce glomerular perfusion and cause ischemic injury, while preglomerular vasodilation may lead to glomerular hypertension and hyperfiltration. RAAS activation is likely central to hypertensive nephropathy in animals.
Normally, autoregulation maintains glomerular capillary pressure at 60–65 mm Hg, but renal disease may impair this, allowing BP fluctuations to directly impact glomerular pressure and filtration—causing ischemia or intraglomerular hypertension. SH may also damage tubular cells, triggering epithelial-mesenchymal transition and tubulointerstitial fibrosis. Ultimately resulting in proteinuria.

Question 21

Describe the pathophysiology of hypertensive encephalopathy in systemic hypertension.

Answer 21

CNS and Autoregulation:
* Autoregulation normally maintains cerebral perfusion pressure constant in response to changes in BP via myogenic reflexive vasoconstriction or dilation.
* Sudden and severe increases in arterial pressure can exceed autoregulatory mechanisms because the arterioles are limited in their ability to constrict.
* Intracerebral BP then increases, and the blood-brain barrier (BBB) is breached.
The result is vascular fluid diffusion across capillary membranes into the brain parenchyma, leading to cerebral edema, increased intracranial pressure, and potentially neurologic deficits.
In chronic SH, the cerebral vasculature undergoes adaptations, such as arteriolar hypertrophy, to allow for a higher autoregulatory range. These changes in cerebral vasculature may result in loss of regulatory tone and changes to vessel walls. A rightward shift in the range of BP needed to maintain constant cerebral blood flow occurs. As a result, reductions in BP may contribute to hypoperfusion and stroke.
Both vascular remodeling and vasoconstriction can induce ischemia and lead to edema with development of hypertensive encephalopathy.

Question 22

What are the clinical signs of hypertensive encephalopathy?

Answer 22

• Seizures
• Altered mentation
• Blindness
• Vestibular
• Cerebellar ataxia
• Pathologic nystagmus.
  Cerebellar herniation has been reported in some patients.

Question 23

What other neurological disorder can occur in cats with systemic hypertension?

Answer 23

SH in cats has also been linked to spinal injury, often presenting acutely with paresis, plegia, or cervical ventroflexion. Ischemic myelopathy, particularly affecting C1–C5 (most commonly C2–C3), results from ventral spinal cord white matter ischemia.

Question 24

What are the treatment goals of systemic hypertension?

Answer 24

Goal is to reduce the risk of target organ damage with a gradual decrease in BP. Rapid reduction in BP should be avoided unless there are signs of target organ damage.

Question 25

Define the categories for BP range and risk of development of target organ damage.

Answer 25

- Normotensive: <140 mm Hg: minimal TOD risk - Prehypertensive: 140-159 mm Hg: low TOD risk - Hypertensive: 160-179 mm Hg: moderate TOD risk - Severely hypertensive: >180 mm Hg: high TOD risk

Question 26

In cases of systemic hypertension, why is a gradual decrease in BP important?

Answer 26

Rapid reduction in BP should be avoided unless there are signs of target organ damage. Because of autoregulatory mechanisms in the body despite normal fluctuations in BP perfusion to the brain, heart and kidneys remains constant. This increases the susceptibility to hypoperfusion, with a 20-25% reduction in the lower threshold for autoregulation.

Question 27

What is the treatment for systemic hypertension in cats?

Answer 27

First-line therapy for oral treatments of SH in cats include amlodipine and telmisartan. The effects of angiotensin-receptor blockers (ARBs) for proteinuric conditions may lead to preferential use in some clinical scenarios. Amlodipine may be preferentially selected in patients with severe SH (SBP >200 mm Hg). Monotherapy is recommended to start and is usually sufficient to control SH.

Question 28

What is the treatment of systemic hypertension in dogs?

Answer 28

1. Benazepril is used for RAAS inhibition in dogs with systemic hypertension (SH). It is especially beneficial for managing proteinuria in dogs with chronic kidney disease (CKD) or protein-losing nephropathies. 2. Telmisartin - not well studied 3. Amlodipine is recommended as a second-line therapy or adjunct to ACEIs in dogs with systemic hypertension (SH). Monotherapy with amlodipine is not advised.

Question 29

Why is monotherapy with amlodipine in dogs not advised?

Answer 29

Monotherapy with amlodipine is not advised due to preferential afferent arteriole dilation, which can increase glomerular capillary pressure, worsening proteinuria and glomerular damage.

Question 30

What is the mechanism of action of amlodipine?

Answer 30

Reduces calcium ion influx through plasma membrane channels resulting in vasodilation in peripheral arterial beds leading to decrease SVR and as MAP = CO x SVR, a decrease MAP.

Question 31

What are the side effects of amlodipine?

Answer 31

Because of amlodipine’s relatively slow onset of action, hypotension and inappetence is usually absent in cats. Infrequently, cats may develop azotemia, lethargy, hypokalemia, reflex tachycardia and weight loss. Monotherapy with amlodipine is not advised due to preferential afferent arteriole dilation, which can increase glomerular capillary pressure, worsening proteinuria and glomerular damage.

Question 32

What is the typical dose use in the treatment of hypertension?

Answer 32

Dogs: 0.2-0.4mg/kg PO q24 Cats: 0.625-1.25mg/cat PO q24

Question 33

What is the mechanism of action of telmisartan?

Answer 33

Monotherapy with amlodipine is not advised due to preferential afferent arteriole dilation, which can increase glomerular capillary pressure, worsening proteinuria and glomerular damage.

Question 34

What is the dose of telmisartan?

Answer 34

Dogs: 1-2 mg/kg PO q24h Cats: 1.5 mg/kg PO q12h loading dose × 14 days, then ↓ to 2 mg/kg PO q24h; or start immediately at 2 mg/kg PO q24h

Question 35

What are the side effects of telmisartan?

Question 36

What is the mechanism of action of benazepril, enalapril etc?

Answer 36

Inhibition of ACE → ↓ formation of ATII and ALDO, leading to ↓ SBP, anti-proteinuric effects, and other systemic effects.

Question 37

What is the dose of benazepril for SH?

Answer 37

Inhibition of ACE → ↓ formation of ATII and ALDO, leading to ↓ SBP, anti-proteinuric effects, and other systemic effects.

Question 38

What classifies a hypertensive emergency in dogs and cats?

Answer 38

SH rarely requires emergency treatment unless there's acute, severe target organ damage (TOD) and SBP >180 mm Hg.

Question 39

What are the treatment goals of hypertensive emergencies?

Answer 39

Reduce SBP by 10% in first hour, 15% over next few hours.

Question 40

What parental medications are used to treat hypertensive emergencies?

Answer 40

- Sodium nitroprusside: Reliable SBP reduction; start at 1–2 mcg/kg/min IV CRI; max 10 mcg/kg/min. - Labetalol: Lowers BP without increasing HR; dose: 0.25 mg/kg IV over 2 min (up to 3.75 mg/kg), then 25 mcg/kg/min CRI. - Hydralazine: Effective; oral: 0.5–2 mg/kg PO q12h; IV in dogs: 0.1 mg/kg over 2 min, then 1.5–5 mcg/kg/min CRI. - Phentolamine: Used in pheochromocytoma; 0.1 mg/kg IV bolus, then 1–2 mcg/kg/min CRI. - Esmolol: Rapid acting; for tachycardic SH, especially in pheochromocytoma (after alpha blockade); 50–75 mcg/kg/min IV CRI. - Magnesium sulfate: Used anecdotally in dogs (e.g. pheochromocytoma); loading dose 30 mg/kg IV, then 15–30 mg/kg/hr. Oral Medications: - Hydralazine and Amlodipine: Used when parenterals unavailable. - Amlodipine: Initial dose 0.25 mg/kg PO, repeat every 1–3 h until SBP is 140–160 mm Hg or max cumulative dose reached. Caution: Doses >0.8 mg/kg/day may cause toxicity; cumulative 1 mg/kg/day dose not recommended.