Hypertension in the Dog and Cat

Preface
Contents
List of Contributors
List of Abbreviations
Part I: Physiology, Pathophysiology and Epidemiology of Hypertension
	1: Physiology of Blood Pressure Regulation and Pathophysiology of Hypertension
		1.1 Introduction
		1.2 The Kidney and Body Fluid Volume Axis
		1.3 Pathophysiological Mechanisms in Regulation of Body Fluid Volume Associated with Hypertension in Dogs and Cats
		1.4 Cardiovascular Influences on Blood Pressure: Regulation of the Heart and Vasculature
		1.5 The Nervous System and Control of Cardiovascular Function
			1.5.1 The Concept of Sympathetic Vascular Tone
			1.5.2 Vagal Tone
			1.5.3 Vasodilator Tone: The Influence of the Endothelium
			1.5.4 Cross-Talk Between the Sympathetic Nervous System, the RAAS and the NO System
			1.5.5 Regulation to Prevent Excessive Vasoconstriction
		1.6 Sympathetic Nervous System Overactivity and Pathophysiology of Hypertension Associated with CKD
		1.7 Endothelial Cell Dysfunction and Hypertension Associated with CKD
		1.8 Reduced Vascular Compliance, Cardiovascular Mineralisation and Hypertension Associated with CKD
		1.9 Conclusions
		References
	2: Measurement of Blood Pressure in Conscious Cats and Dogs
		2.1 Importance of Accurate Blood Pressure Measurement
		2.2 Validation for Blood Pressure Monitoring Devices in Human and Veterinary Medicine
		2.3 Calibration of Blood Pressure Monitoring Devices
		2.4 Direct Arterial Blood Pressure Monitoring
		2.5 Indirect Blood Pressure Monitoring
		2.6 Oscillometry
			2.6.1 Oscillometric Measurement in Dogs and Cats
			2.6.2 High-Definition Oscillometry in Dogs and Cats
		2.7 Doppler Sphygmomanometry
		2.8 Cuffless Blood Pressure Monitoring
		2.9 Practical Aspects of Blood Pressure Measurement in the Clinic
			2.9.1 Location for Performing Blood Pressure Measurement and Acclimatisation
			2.9.2 Obtaining Multiple Measurements
			2.9.3 Timing of Assessment of Blood Pressure
			2.9.4 Position of the Patient for Blood Pressure Measurement
			2.9.5 Position of the Cuff for Blood Pressure Assessment
			2.9.6 Size of Cuff for Blood Pressure Assessment
			2.9.7 Accurate Recording of Blood Pressure Measurement in Clinical Records
		2.10 Patient-Associated Factors Influencing Accuracy of Blood Pressure Measurement
		2.11 Clinical Protocols for Blood Pressure Measurement for the Diagnosis of Hypertension
		References
	3: Epidemiology of Hypertension
		3.1 Dichotomising Blood Pressure into Hypertension and Normotension Categories
			3.1.1 Humans
			3.1.2 Dogs and Cats
		3.2 Epidemiological Associations with Adverse Outcomes/Target Organ Damage
			3.2.1 Humans
			3.2.2 Dogs and Cats
		3.3 Effect of Patient Characteristics (Age, Breed and Sex)
			3.3.1 Humans
			3.3.2 Dogs and Cats
		3.4 Obesity and Dietary Factors
			3.4.1 Humans
			3.4.2 Dogs and Cats
		3.5 Primary and Secondary Hypertension
			3.5.1 Humans
			3.5.2 Dogs and Cats
		3.6 White-Coat, Situational and Masked Hypertension
			3.6.1 Humans
			3.6.2 Dogs and Cats
		3.7 Diurnal Variation
			3.7.1 Humans
			3.7.2 Dogs and Cats
		References
	4: Hypertension and Adrenal Gland Disease
		4.1 Hyperadrenocorticism
			4.1.1 Epidemiology of Hypertension Associated with Hyperadrenocorticism in Dogs and Cats
			4.1.2 Pathophysiology of Hypertension in Hyperadrenocorticism
			4.1.3 Treatment of Hypertension in Dogs and Cats with Hyperadrenocorticism
		4.2 Pheochromocytoma and Paraganglioma
			4.2.1 Epidemiology of Hypertension Associated with Pheochromocytoma and Paraganglioma
			4.2.2 Pathophysiology of Hypertension in Pheochromocytoma and Paraganglioma
			4.2.3 Treatment of Hypertension Associated with Pheochromocytomas and Paragangliomas
		4.3 Hyperaldosteronism (Conn´s Syndrome)
			4.3.1 Epidemiology of Hypertension Associated with Hyperaldosteronism in Dogs and Cats
			4.3.2 Pathophysiology of Hypertension Associated with Hyperaldosteronism
			4.3.3 Treatment of Hypertension in Dogs and Cats Associated with Hyperaldosteronism
		References
	5: Thyroid Gland Disease
		5.1 Physiological Effects of Thyroid Hormones on the Cardiovascular System
		5.2 Effect of Hyperthyroidism on Blood Pressure in Humans
		5.3 Effect of Hypothyroidism on Blood Pressure in Humans
		5.4 Hypertension in Dogs and Cats with Hyperthyroidism
			Clinical Recommendations
		5.5 Hypertension in Dogs and Cats with Hypothyroidism
		5.6 Conclusions
		References
	6: Genetics of Hypertension: The Human and Veterinary Perspectives
		6.1 Mendelian Blood Pressure Syndromes
		6.2 Hypertension as a Complex Disease Trait
			6.2.1 Mendelian Genes and Their Association with Population Blood Pressure
			6.2.2 Development of Genome-Wide Association Studies and Exploration of Population Blood Pressure
			6.2.3 Genetics of Blood Pressure in the Dog and the Cat
		References
Part II: Clinical and Pathological Consequences of Hypertension
	7: Hypertension and the Kidney
		7.1 Does Hypertension Contribute to Proteinuria in Dogs and Cats: What Is Known from Experimental Models?
		7.2 Does Hypertension Lead to Increased Proteinuria and Progressive Renal Injury in Canine and Feline Clinical Cases of Hypert...
		7.3 Renal Pathology Associated with Hypertension in Naturally Occurring Kidney Disease
		7.4 Summary
		References
	8: Hypertension and the Heart and Vasculature
		8.1 Introduction
		8.2 Pathologic Changes to the Cardiovascular System in Systemic Hypertension
			8.2.1 The Heart as a Target Organ
			8.2.2 The Systemic Vasculature as a Target Organ
		8.3 Mechanisms of Cardiovascular Target Organ Damage in Systemic Hypertension
		8.4 Clinical Implications of Cardiac Target Organ Damage in Hypertensive Veterinary Patients
		8.5 Clinical Cardiovascular Findings in Hypertensive Veterinary Patients
		8.6 Expected Response to Treatment of Hypertensive Cardiac Target Organ Damage
		8.7 Conclusions
		References
	9: Hypertension and the Eye
		9.1 Introduction
		9.2 Ocular Blood Flow
			9.2.1 Autoregulation
			9.2.2 Blood-Retinal Barrier
		9.3 Pathophysiology
		9.4 Pathology
		9.5 Ocular Manifestations of Systemic Hypertension
			9.5.1 Hypertensive Retinopathy
			9.5.2 Hypertensive Choroidopathy
			9.5.3 Hypertensive Optic Neuropathy
		9.6 The Clinical Picture
			9.6.1 Signalment
			9.6.2 Ocular Examination
			9.6.3 Prevalence of Ocular Lesions
			9.6.4 Differential Diagnosis for Hypertensive Ocular Lesions
			9.6.5 Blood Pressure
			9.6.6 Concurrent Disease
		9.7 Treatment
		9.8 Prognosis
		9.9 Conclusion
		References
	10: Hypertension and the Central Nervous System
		10.1 Introduction
		10.2 Basic Vascular Physiology of the CNS: Blood Supply and Autoregulation
		10.3 Pathophysiological Mechanisms of Chronic Hypertension in the CNS
		10.4 Acute HE: Breaking Through and Breaking Down
		10.5 Hypertension and Seizures
		10.6 Clinical Presentation and Diagnosis of Hypertensive Brain Lesions in Dogs and Cats
		10.7 Treatment and Prognosis
		10.8 Conclusion
		References
Part III: Pharmacology and Therapeutic Use of Antihypertensive Drugs
	11: Pharmacology of Antihypertensive Drugs
		11.1 Introduction
		11.2 Antihypertensive Drug Targets
			11.2.1 Sympathetic Nervous System
			11.2.2 The Renin-Angiotensin-Aldosterone System
				11.2.2.1 Non-ACE Pathways for Angiotensin II Formation
				11.2.2.2 ACE Inhibitors
				11.2.2.3 Pharmacokinetics of ACE Inhibitors
				11.2.2.4 Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of ACEi
				11.2.2.5 Angiotensin Receptor Blockers
				11.2.2.6 Mineralocorticoid Receptor Antagonists
					Rationale for Use of Aldosterone Receptor Blockers with ACE Inhibitors
					Use of Aldosterone Receptor Antagonists in Veterinary Patients
					Clinical Evidence of Efficacy and Safety of Spironolactone in Dogs
					Clinical Evidence of Efficacy and Safety of Spironolactone in Cats
			11.2.3 Calcium Channel Blockers
				11.2.3.1 Evidence of the Blood Pressure Lowering Effect of Amlodipine in Veterinary Species
				11.2.3.2 Pharmacokinetics of Amlodipine in Cats
				11.2.3.3 Pharmacodynamic Effects of Amlodipine in Cats: Experimental Studies
				11.2.3.4 Clinical Trials to Determine the Antihypertensive Effect of Amlodipine in Feline Patients
		11.3 Overall Conclusions
		References
	12: Management of Hypertension in Cats
		12.1 Introduction
		12.2 Confirming a Diagnosis of Systemic Hypertension
		12.3 Interpreting SBP Results
			12.3.1 SBP  180 mmHg: Severe Hypertension with Severe Risk of TOD
			12.3.2 SBP 160-179 mmHg: Hypertension with Moderate Risk of TOD
			12.3.3 SBP 140-159 mmHg: Prehypertension with Mild Risk of TOD
			12.3.4 SBP Less than 140 mmHg: Normotension
		12.4 Management of Hypertensive Cats
		12.5 Management of Patients with Concurrent Disease
		12.6 Prognosis
		References
	13: Management of Hypertension in Dogs
		13.1 Introduction
		13.2 Diagnosis of SH
			13.2.1 Situational Hypertension
			13.2.2 Idiopathic Hypertension
			13.2.3 Secondary Hypertension
		13.3 Decision to Institute Therapy
		13.4 Initial Assessment of a Dog with SH
			13.4.1 Assessment for TOD
			13.4.2 Investigations for Causes of Secondary Hypertension
		13.5 Goals of Therapy
		13.6 General Recommendations for the Management of SH
			13.6.1 Patient Monitoring
			13.6.2 Dietary Therapy
			13.6.3 Initial Antihypertensive Drug Therapy
				13.6.3.1 RAAS Inhibitors
				13.6.3.2 Amlodipine
			13.6.4 Combination Antihypertensive Therapy
			13.6.5 Management of Dogs with Refractory Hypertension
				13.6.5.1 Alpha-Adrenergic Receptor Antagonists
				13.6.5.2 Beta-Adrenergic Receptor Antagonists
				13.6.5.3 Mineralocorticoid Receptor Antagonists
				13.6.5.4 Hydralazine
				13.6.5.5 Diuretics
			13.6.6 Adverse Effects of Antihypertensive Medications and Their Management
		13.7 Management of a Hypertensive Crisis
		13.8 Management of SH in Specific Conditions
			13.8.1 Renal Disease
				13.8.1.1 Chronic Kidney Disease
				13.8.1.2 Acute Kidney Disease
				13.8.1.3 Other Renal Diseases
			13.8.2 Hyperadrenocorticism
			13.8.3 Pheochromocytoma
			13.8.4 Diabetes Mellitus
			13.8.5 Hyperaldosteronism
			13.8.6 Thyroid Disease
			13.8.7 Cardiovascular Disease
			13.8.8 Circulatory Volume Overload
		13.9 Potential Future Therapeutic Options
		13.10 Summary
		References
Part IV: Future Perspectives
	14: Future Perspectives
		References