How does cortisol affect blood pressure?

Cortisol's Effects on Blood Pressure

Cortisol increases blood pressure through multiple mechanisms including sodium retention, vascular sensitivity, and inhibition of vasodilatory pathways. This relationship is well-documented in both pathological states like Cushing syndrome and with exogenous cortisol administration.

Primary Mechanisms of Cortisol-Induced Hypertension

Sodium and Volume Effects

• Cortisol causes significant sodium retention and volume expansion 1
• However, sodium retention is not the primary mechanism, as blocking mineralocorticoid receptors with spironolactone does not prevent cortisol-induced hypertension 1
• Cortisol administration increases body weight, suggesting fluid retention 2

Vascular Effects

• Cortisol inhibits cholinergic vasodilation in human forearm circulation 3
• Suppression of the nitric oxide system appears to play a key role in cortisol-induced hypertension 1, 3
• Patients with essential hypertension show increased vasoconstrictor sensitivity to glucocorticoids compared to normotensive individuals 4

Sympathetic Nervous System

• Direct and indirect measures of sympathetic activity are unchanged or suppressed during cortisol administration 1
• Cortisol may affect blood pressure by altering adrenergic activity or suppressing parasympathetic neural activity 5

Magnitude and Timing of Blood Pressure Effects

• Oral cortisol increases blood pressure in a dose-dependent manner 1
• At doses of 80-200 mg/day, peak increases in systolic pressure are approximately 15 mmHg 1
• Blood pressure increases become apparent within 24 hours of cortisol administration 1
• In one study, cortisol (200 mg/day for 5 days) significantly increased:
  • Systolic BP from 113±3 to 130±4 mmHg
  • Diastolic BP from 65±3 to 81±2 mmHg
  • Mean arterial pressure from 81±2 to 97±3 mmHg 2

Clinical Relevance

Cushing Syndrome

• Hypertension is present in 70-90% of patients with Cushing syndrome 5
• Approximately 17% of Cushing syndrome patients have severe hypertension 5
• Target organ damage in Cushing syndrome is more severe than in primary hypertension 5
• The main mechanism of hypertension in Cushing syndrome is overstimulation of mineralocorticoid receptors by cortisol, though sleep apnea and insulin resistance also contribute 5

Resistant Hypertension

• Mineralocorticoid receptor antagonists (spironolactone or eplerenone) are the most effective antihypertensive agents in Cushing syndrome 5
• Surgical excision of ACTH- or cortisol-producing tumors effectively lowers blood pressure 5

Physiological Relevance

• Even within physiological ranges, higher morning serum cortisol is associated with vascular risk markers in prepubertal children, including increased systolic blood pressure and carotid intima-media thickness 6
• This association is independent of age, BMI, body fat, waist, insulin resistance, serum lipids, and heart rate 6

Potential Role in Essential Hypertension

• Vasoconstrictor sensitivity to glucocorticoids is increased in essential hypertension 4
• This increased sensitivity may initiate or sustain the increased peripheral vascular resistance characteristic of essential hypertension 4
• 11β-dehydrogenase activity (which inactivates cortisol) is impaired in essential hypertension 4

Conclusion

Cortisol significantly impacts blood pressure regulation through multiple mechanisms, primarily affecting vascular tone and sodium handling. These effects are relevant not only in pathological states like Cushing syndrome but may also play a role in essential hypertension. The relationship between cortisol and blood pressure begins rapidly after exposure and appears to be dose-dependent.