Week 4

Hypertension
Learning Objectives
I.

Normal Blood Pressure Regulation

A. Describe the relationship of cardiac output/total peripheral resistance to
blood pressure.
B. Explain the role of abnormal pressure natriuresis and sodium sensitivity
in the development of hypertension
C. Review ECV control (afferent limb of volume sensing-atrial filling, baroreceptors, and afferent renal blood flow/pressure, etc.), renal mechanisms
responsible for sodium balance (neuro-humoral, tubulo-glomerular
feedback, myogenic response, and nephronal sites of regulation of sodium
reabsorption). [Week 2]

II.

Systemic and Cellular Mechanisms Involved in the Pathogenesis of

Hypertension
A. Describe the role of Renin-Angiotensin System-dysregulation with renal
blood flow, sodium balance, and experimental Goldblatt hypertension.
Explain why most subjects with hypertension have no demonstrable
abnormality of the Renin-Angiotensin-Aldosterone axis.
B. Explain role of increased peripheral vascular resistance in the maintenance
phase of hypertension including:
1. The Endothelium: Nitric Oxide/Endothelin and other Vasoactive
substances
2. Vascular Smooth Muscle: Sympathetic Nervous System, Human
Ouabain-like Hormone, Intracellular Ca+2 and Membrane Transport
Abnormalities (Na+: Ca+2 and Na+/H+ Exchange)
C. Defend the difference between normal blood pressure regulation and
hypertension

III.

Genetics of Hypertension
A. Describe familiar inheritance patterns(Polygenetic)
B. Evaluate experimental models (Genetic Knock-outs and Transgenics) and
clinicalassociations (Polymorphisms-ACE and Angiotensin Receptors) of
hypertension
C. Assess hypertension in the Metabolic Syndrome of Obesity and Insulin
Resistance

IV.

Differentiate secondary forms of hypertension and understand

mechanisms including:
A. Primary Excess Mineralocorticoids (Aldosterone)
B. Primary Renal Sodium Retention-Na+ Channel (ENaC)-Liddles Syndrome
C. Renal Vascular Hypertension
D. Renal Insufficiency
E. Increased Catecholamines (Endogenous and Exogenous)

V.
Compare the mechanisms of action, clinical uses, side-effects and
pharmacokinetics of the following classes of antihypertensive agents:
A. Ace Inhibitors and Angiotensin Receptor Blockers
B. Alpha- and Beta-Adrenergic Receptor Blockers

C.
D.
E.
F.

Diuretics
Ca+2 Channel Blockers
Centrally-acting Alpha-2 Agonists
Direct Vasodilators

VI.

Analyze the clinical evaluation of an individual with hypertension that

is cost effective (history, physical examination, and
laboratory/imaging studies)

VII.

Assess the natural history of untreated and treated hypertension.

Defend role of life style modifications (weight, exercise, diet, alcohol
intake, and smoking) in reducing adverse outcomes in hypertension