Hypertension and RAAS Flashcards
How and when should BP be measured in a dog/cat during a visit?
In a quiet area, away from other animals, before other procedures, and after the patient has acclimated for 5-10 minutes. Owner should be present and restraint should be minimal, but the patient should be in ventral or lateral recumbency
What should the width of the BP cuff be?
30-40% of the circumference of the extremity at the site of cuff placement
How many BP measurements should be obtained?
Discard the first measurement. Then 5-7 consecutive, consistent readings
If BP is trending downward as the animal adjusts, continue until a plateau is reached, then take 5-7 readings
If the vertical distance from the heart to the base of the cuff is more than 10cm, what correction can be applied?
Add 0.8 mmHg/cm below or above the heart base
Blood pressure in hounds (Greyhounds, Deerhounds) is how much higher than other dogs?
10-20mmHg higher
What is situational hypertension?
Increases in BP that occur as a consequence of the in clinic measurement process in an otherwise normotensive animal
What causes situation hypertension?
Autonomic nervous system alterations
What is secondary hypertension?
Persistent, pathologically increased BP concurrent with a disease or condition known to cause hypertension or administration of a drug or toxin known to cause hypertension
Name 6 disease conditions associated with secondary hypertension
CKD, AKI, hyperadrenocorticism, DM, primary hyperaldosteronism, pheochromocytoma, hyperthyroidism
Name 5 drugs associated with secondary hypertension
Glucocorticoids, mineralocorticoids, EPO, PPA, Ephedrine/pseudoephedrine, Palladia
What is primary/essential/idiopathic hypertension?
Persistent, pathological hypertension in the absence of any identifiable underlying cause
How can BP affect USG?
Hypertension can cause polyuria from pressure diuresis, so a USG <1.030 in a patient with hypertension does not necessarily mean that CKD is present
What percent of cats have idiopathic hypertension?
13-20%
How can hypertension affect the kidneys?
Causes proteinuria and histological renal injury. Proteinuria, in turn, leads to more rapid progression of renal disease
What are the findings with hypertensive retinopathy and choroidopathy?
Exudative retinal detachment - most common
Retinal hemorrhage or edema, retinal vessel tortuosity, vitreal hemorrhage, hyphema, secondary glaucoma, and retinal degeneration
What is hypertensive encephalopathy?
White matter edema and vascular lesions from hypertension
When is hypertensive encephalopathy more likely to occur?
Cats with a sudden increase in BP, systolic BP >180 mmHg, or both
What are the clinical signs of hypertensive encephalopathy?
Lethargy, seizures, acute onset of altered mentation, altered behavior, disorientation, vestibular signs
Hypertension is also a risk factor for ischemic myelopathy of the cranial cervial spinal cord. How does this present?
Cats with ambulatory tetraparesis or tetraplegia with intact nociception
What is the most common cardiac change associated with hypertensive cardiomyopathy?
Left ventricular concentric hypertrophy
What are the indications for measuring BP in a dog or cat?
- Patients with clinical abnormalities consistent with hypertensive target organ damage
- The presence of diseases or conditions or the treatment with drugs associated with secondary hypertension
In the majority of cases, BP results should be repeated on >2 occasions before starting treatment. What is the exception?
When there is evidence of target organ damage along with an elevated BP - start treatment now
What are the classifications of hypertension in dogs/cats?
Normotensive: SBP < 140
Prehypertensive: SBP 140-159
Hypertensive: SBP 160-179
Severely hypertensive: SBP >180
If a patient’s BP is <160 mmHg, when should they be rechecked?
3-6 months
If a patient’s BP is 160-179 mmHg with no evidence of target organ damage, when should they be rechecked?
Repeat BP twice within 4-8 weeks
- If repeatedly above 160, look for underlying causes and start antihypertensives
If a patient’s BP is >180 mmHg with no evidence of target organ damage, when should they be rechecked?
Repeat BP twice within 2 weeks
- If repeatedly above 160, look for underlying causes and start antihypertensives
After starting antihypertensive medication, when should the BP be rechecked?
7-10 days if no TOD
1-3 days if TOD is present
What is the goal of antihypertensive therapy?
Optimal goal: BP <140 mmHg
Minimal goal: BP <160 mmHg
If you achieve the goals of antihypertensive therapy, when should you recheck the patient?
Every 4-6 months
A RAAS inhibitor can be used as the first line anti-hypertensive treatment in dogs, except in what situation?
Severe hypertension (BP >200) - start BOTH a RAAS inhibitor and CCB
Why should a CCB not be used as monotherapy in hypertensive dogs?
CCB preferentially dilate the renal afferent arteriole, increasing glomerular capillary hydrostatic pressure and worsening proteinuria
Amlodipine is the first line therapy for hypertensive cats. What decrease in BP does it typically cause?
28-55 mmHg
What is the starting dose of amlodipine in cats?
If SBP <200mmHg, 0.625 mg/cat
If SBP >200mmHg, 1.25mg/cat
What decrease in BP is seen in cats on ACEi?
Small - <10mmHg
Not useful as a single agent, but can be used with amlodipine
What adverse effects have been noted with spironolactone in cats?
Facial dermatitis and excoriation (rare)
In patients with acute hypertensive emergencies (TOD), what is the therapeutic target? Why?
Small, incremental decrease in SBP rather than normalization - decrease by 10% over the first hour and 15% over the next few hours
In chronic hypertension, the autoregulatory vascular beds in the brain and kidneys have adapted to higher perfusion pressure; acute marked BP reductions may result in hypoperfusion
Due to the requirement for incremental SBP decreases in a hypertensive crisis, what types of agents should be used?
Parenteral drugs that can be titrated to effect with rapid onset and rapid conclusion of action
What is fenoldopam?
Dopamine-1 receptor agonist approved for human hypertensive emergencies - causes renal arterial vasodilation, natriuresis, and increased GFR
Apart from fenoldopam, what other drugs can be used in a hypertensive crisis?
Hydralazine, nitroprusside, labetolol
What percent of cats with AKI were hypertensive?
59%, severe (>180) in 28% - was not correlated with grade of AKI, creatinine, oliguria or anuria
What is angiotensin converting enzyme 2?
Homologue of ACE but produces angiotensin peptides (angiotensin 1-9 and 1-7) that are vasodilatory and natriuretic - counterbalance angiotensin II
In a study of 780 healthy cats, what factors were associated with higher systolic BP?
Increased age, male sex, increased nervousness, history of being a stray, neutering
How does the BP of Birman’s differ from other cat breeds?
Lower (125 vs 140)
Absent metatarsal pulses correctly identify cats with a SBP of 75mmHg or less what percent of the time?
84%
Absent metatarsal and femoral pulses correlated with a SBP of what?
30mmHg on average
Did treatment of CKD in dogs with benazepril improve survival time in a randomized clinical trial?
No - MST 305 for benazepril and 287 for placebo
Did proteinuria improve with treatment of CKD dogs with benazepril in a randomized clinical trial?
Yes - but not that much
All dogs: UPC 1.51 benazepril vs 1.94
Dogs with UPC >0.5: UPC 1.76 benazepril vs 2.98
Compared to placebo, telmisartan (1-3mg/kg/day) had what affect on SBP in cats?
- Decreased SBP at all dosages by two weeks after initiation of treatment
- SBP remained decreased for 2 days after stopping telmisartan
- No hypotensive events
In a prospective, randomized, blinded European trial, what effect did telmisartan have on the BP of 252 cats
By day 14, telmisartan decreased SBP from 180 mmHg by 19 mmHg
By day 28, decreased SBP by 25 mmHg
Placebo group decreased by 9 and 11
In a prospective, randomized, blinded European trial, what percent of telmisartan cats had achieved an SBP <150mmHg by day 28?
52%
In a prospective, randomized, blinded European trial, how long did the effects of telmisartan on BP last?
For the entire study period - up to 120 days after initiation of treatment
In a prospective, randomized, blinded European trial, how many cats on telmisartan experienced hypotension?
2 out of 252
What factor influenced the dose of amlodipine needed to control BP in cats?
The initial SBP - cats that needed 0.625mg had a median SBP 182 vs 207 in cats that needed 1.25mg
In a prospective, randomized, blinded American trial, what was the SBP decrease in cats on telmisartan by day 14?
Telmisartan decreased BP by 23mmHg compared to 7.5 in the placebo group
Similar results at day 28
In a prospective, randomized, blinded American trial, how long did the decrease in SBP persist while on telmisartan?
The entire study period - 6 months of follow up
Where is renin synthesized? What form is it synthesized in?
- In the juxtaglomerular epithelioid cells
- Synthesized as preprorenin, which is cleaved to prorenin, then renin
What is the rate limiting step in the RAAS cascade?
Release of renin granules - released in a controlled manner, unlike angiotensinogen, which is constitutively released from the liver
What factors trigger renin release?
- Low systemic BP
- Hypovolemia
- Sodium deprivation
- Sympathetic stimulation
What is the function of renin in circulation?
Metabolizes angiotensinogen to angiotensin I
Where is angiotensin converting enzyme released and what is it’s function?
- Released from endothelial cells
- Convers angiotensin I to angiotensin II
When angiotensin II binds to angiotensin type 1 receptors, what effects occur?
- Sodium retention
- Vasoconstriction (including preferential constriction of the efferent arteriole)
- Stimulation of thirst
- Enhanced sympathetic nervous system activity
- Aldosterone release
Where is aldosterone released from?
The zona glomerulosa of the adrenal glands
When angiotensin II binds to angiotensin type 2 receptors, what effects occur?
Counter regulatory to the actions of the type 1 receptor - anti-inflammatory, anti-fibrotic, vasodilatory
What two things stimulate aldosterone release?
Angiotensin II
Increased extracellular K+ concentrations
Aldosterone acts on mineralocorticoid receptors. Where are these located?
Kidney, colon, salivary and sweat glands
What is the ultimate function of aldosterone?
Increase in transepithelial Na+ and water reabsorption, K+ excretion
Aldosterone and angiotensin peptides are also produced locally in tissues. What roles do locally produced RAAS hormone have?
- Play important roles in normal cardiovascular function and electrolyte-fluid balance
- Mediate abnormal remodeling (hypertrophy and fibrosis) of tissues
Local (tissue) activity of aldosterone can be stimulated by what factors?
- Mechanical stretch of the myocardium and vessels
- Adipocyte secretions
- ROS and inflammation
Angiotensin II increases sodium reabsorption in what renal tubules?
Proximal tubule and loop of Henle
ACEi not only decrease formation of angiotensin II, but they decrease the degradation of what vasodilatory compound?
Bradykinin
In local tissues, what enzyme is more important than ACE for conversion of angiotensin?
Chymase
Clinical trials evaluating the use of ACEi in dogs with CHF showed that ACEi improved what factors?
- Improvement in pulmonary edema score
- Improvement in pulmonary capillary wedge pressure
- Improvement in cough
- Improvement in survival time and delay to worsening of CHF
In a double blinded study of dogs with MMVD Stage B2, treatment with enalapril improved what?
All cause mortality
Another study evaluating Cavaliers with B1 or B2 MMVD showed what difference between enalpril and placebo?
No difference in the onset of CHF
