Several lines of evidence implicate sympathetic nervous system involvement in the pathophysiology of essential hypertension in man. Extrapolations are frequently made from in vitro measurements of plasma catecholamine levels to the physiologic role of the sympathetic system in hypertension. We assessed the utility and validity of such extrapolation from in vitro to in vivo measures of adrenergic function. Addition of guanadrel to diuretic therapy in 11 patients with essential hypertension reduced supine intra-arterial blood pressure from 135 +/- 14/76 +/- 9 to 127 +/- 13/67 +/- 5 mm Hg (P less than 0.02). Supine heart rate was also reduced, from 77 +/- 14 to 63 +/- 13 bpm (P less than 0.001). Plasma norepinephrine levels fell from 303 +/- 107 to 170 +/- 46 pg/ml (P less than 0.01). Platelet alpha 2-receptor number ([3H]yohimbine maximal binding) increased from 204 +/- 77 to 301 +/- 150 fmol/mg (P less than 0.02). The pupillary mydriatic response to phenylephrine and the forearm arterial vasoconstrictor response to intra-arterial norepinephrine did not change. Thus guanadrel reduced blood pressure by decreasing sympathetic tone. In this milieu of low sympathetic activity the platelet alpha 2-receptor number increased, but physiologic responses to exogenous alpha-agonists did not change. Caution is therefore advised when extrapolating from in vitro measurement of plasma catecholamine levels and platelet alpha 2-receptor number to the in vivo physiologic significance.

This study tested the hypothesis that the Type A behavior pattern and its components are associated with increased activity of the sympathetic nervous system. To do this, we employed two new markers of sympathetic tone-pupil size and platelet catecholamine content. Thirtythree healthy males were blindly rated for Type A behavior and verbal stylistic components by Structured Interview. Adrenergic tone to the pupils was assessed from pupil diameter recorded by infrared television pupillometry, and pupil alpha-adrenergic sensitivity was estimated from mydriatic response to ophthalmic phenylephrine. Platelet epinephrine and norepinephrine contents were assayed because these levels are associated with chronic, long-term circulating catecholamine levels. The results showed Type As had consistently larger pupil diameters than Type Bs (p = 0.03,0.03, and 0.01). There was no difference in pupillary response to phenylephrine instillation between groups, Platelet epinephrine content was greater in Type A subjects (x 2 = 4.25, p < 0.04, t = 1.6, p = 0.06). Only the component of explosiveness was modestly associated with resting pupil size, and no components significantly predicted platelet catecholamines. We conclude that the results of these two new markers of autonomic activity, namely, pupil size and platelet epinephrine, suggest that Type A behavior is characterized by increased sympathetic nervous system tone although we cannot rule out the possibility of decreased activity of the parasympathetic nervous system.

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Background Recently increased left atrial systolic force (LASF), a measure of left atrial function, has been associated with left ventricular hypertrophy (LVH) in hypertensive patients. Impaired left ventricular relaxation is often seen in hypertensive patients and because of the correlated left ventricular filling impairment the atrial contribution to ventricular filling is important. LASF may increase as a compensatory response to preserve a sufficient stroke volume, which partly could explain the association between age-related prolonged left ventricular relaxation and increased LASF. Reduced left atrial function has also been shown to be associated with poor prognosis in patients with atrial fibrillation. It remains unknown whether LASF can be used as a predictor of new-onset atrial fibrillation (NOAF). Furthermore, the influence of treatment with atenolol and losartan on LASF is unclear. Purpose We aimed to determine whether LASF correlates to incident atrial fibrillation and whether the preservation of LASF reduces the risk of new onset atrial fibrillation (NOAF). Methods N=758 patients without atrial fibrillation at baseline were enrolled from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography sub study. Participants of the LIFE-study were randomized to either atenolol- or losartan-based treatment. Mean follow-up was 59 month. LASF was calculated using average mitral orifice area and mitral peak A velocity obtained by Doppler echocardiography. Results At baseline 25% of patients had a LASF≤10.3kdyn. Compared to other quartiles this quartile had a higher proportion of men, lower heart rate, body mass index and age. After controlling for these variables patients in the first quartile had lower stroke volume compared to other quartiles. New-onset AF occurred in 29 (8.1/1,000 patients-years of follow-up) patients. In multivariable Cox regression analyses with backwards elimination increasing LASF was associated with lower risk of NOAF (HR=0.90 [95% confidence interval 0.85–0.96], p=0.001). Integrated discrimination improvement was 0.054 (p=0.004) and there was a borderline significant net reclassification improvement of 19.2% (p=0.075). Over time LASF decreased more in the atenolol-based than the losartan-based treatment group (p&lt;0.001). Conclusions Low left atrial systolic force (LASF) was associated with higher risk of NOAF. Losartan-based treatment was associated with better preservation of LASF compared to atenolol-based treatment. Our data thus suggest that hypertensive patients with LVH and low LASF identifies a patient group with progressed left atrial dysfunction and with high risk of NOAF. Because of the preserving effect of losartan on the function and structure of the left atrium, treating hypertensive patients with LVH with losartan might decrease their risk of incident atrial fibrillation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The LIFE study originally received support from Merck & Co., Inc.