Related Experiment Videos
Increased coronary vascular resistance cannot be reduced by inhibiting sympathetic overactivity in hypertension
Jan Sundell1, Hanna Laine, Matti Luotolahti
1Turku PET Centre, Turku University, Turku, Finland. jan.sundell@utu.fi
Insights
Hypertensive individuals exhibit sympathetic overactivity, which dexamethasone can normalize. However, increased coronary vascular resistance in hypertension persists after treatment, indicating other contributing factors beyond sympathetic vasoconstriction.
Area of Science:
- Cardiovascular Physiology
- Hypertension Research
- Pharmacology
Background:
- Hypertension is associated with increased sympathetic nervous system activity.
- Elevated coronary vascular resistance (CVR) is a hallmark of hypertension.
- The role of sympathetic overactivity in hypertension-related CVR requires further investigation.
Purpose of the Study:
- To determine if dexamethasone, a central sympathetic inhibitor, can reduce elevated CVR in hypertensive patients.
- To investigate the impact of normalizing sympathetic activity on coronary hemodynamics in hypertension.
Main Methods:
- Positron emission tomography (PET) with [(15)O]H(2)O was used to quantify CVR in 11 hypertensive and 23 normotensive men.
- Measurements were taken at baseline and during adenosine-induced hyperemia.
- Subjects received either dexamethasone or placebo for two days before repeat measurements.
Main Results:
- Hypertensive subjects showed higher baseline plasma norepinephrine and CVR compared to normotensive controls.
- Dexamethasone treatment significantly reduced plasma norepinephrine in hypertensive subjects to normotensive levels.
- Despite normalized norepinephrine, coronary vascular resistances remained significantly elevated in hypertensive individuals post-treatment.
Conclusions:
- Hypertensive subjects exhibit sympathetic overactivity, which dexamethasone effectively normalizes.
- Increased coronary vascular resistance in hypertension is not solely mediated by sympathetic overactivity.
- Other non-sympathetic mechanisms contribute to elevated CVR in hypertensive individuals.
Abstract:
The aim of this study was to test whether increased coronary vascular resistance in hypertensive subjects can be reduced by centrally inhibiting sympathetic overactivity with dexamethasone. Coronary vascular resistance was quantitated in 11 men with untreated mild essential hypertension (RR 149 +/- 13/98 +/- 10 mm Hg) and 23 healthy, normotensive, otherwise matched men using positron emission tomography and [(15)O]H(2)O. The measurements were performed at baseline and during adenosine stimulation. Each subject was studied twice, with and without previous dexamethasone treatment for two days (0.5 mg x 4 per day). Before dexamethasone treatment, cardiac index and plasma norepinephrine concentration (1.9 +/- 0.6 vs. 1.3 +/- 0.5 nmol/l, p < 0.01) were significantly higher in hypertensive than in normotensive subjects. Additionally, both baseline and hyperemic coronary vascular resistances were higher in hypertensive than normotensive subjects (147 +/- 31 vs. 113 +/- 24 and 36 +/- 9 vs. 25 +/- 10 mm Hg.min.g.ml(-1); p < 0.05). Dexamethasone treatment significantly decreased plasma norepinephrine concentrations in hypertensive subjects, leading to comparable plasma norepinephrine concentrations in hypertensive and normotensive subjects (1.4 +/- 0.5 vs. 1.2 +/- 0.4 nmol/l; NS). However, coronary vascular resistances remained increased in hypertensive subjects. In conclusion, hypertensive subjects are characterized by sympathetic overactivity, which can be normalized by dexamethasone. However, coronary vascular resistances remained increased in hypertensive subjects after dexamethasone treatment, suggesting that other mechanisms than sympathetic overactivity-induced vasoconstriction explain the increased coronary vascular resistance in hypertension.