Finding the best method of assessing sympathetic nervous system (SNS) integrity is important to the diagnosis and treatment of several diseases and is the primary goal of this study. Two methods currently used to evaluate SNS activity involve norepinephrine (NE) measurements and each has attributes and shortcomings. The simpler and much more commonly used of the 2 involves measuring """"""""levels"""""""" of plasma NE while the subject is resting supine and upon standing-up. A comparison of these measures reflects SNS responsivity and is a useful diagnostic tool. However, plasma NE levels are the result of 3 processes: 1) NE release (RR) from sympathetic nerve endings, 2) its removal or clearance (Cl) from the body and 3) its distribution (V) throughout the body including selective uptake by specific tissues. The """"""""levels"""""""" methods cannot provide information about RR, Cl, and V, which in some situations may be necessary to detail an SNS defect and to effectively design pharmacotherapy. The second technique, which is less well established and more expensive and complex, allows for calculation of NE pharmacokinetics. This method is accomplished by either a """"""""constant infusion"""""""" or """"""""bolus"""""""" infusion of tritiated NE. Using a within-subjects counterbalanced design to compare the techniques in normal controls and in patients with altered SNS function, this protocol will accomplish 5 goals. 1) We will determine which infusion technique is superior for defining NE pharmacokinetics. Using the infusion technique, we will define NE pharmacokinetics in normal subjects. 2) We will determine whether one method or a combination of the """"""""levels"""""""" and """"""""infusion"""""""" methods is most advantageous for use in the clinic to evaluate SNS function. 3) We will further define the specific SNS defects (in terms of NE pharmacokinetic alterations) in disorders such as thyroid disease, congestive heart failure, neurologically based orthostatic hypotension (OH), pulmonary hypertension and some specific subtypes of essential hypertension. 4) We will better delineate mechanisms of action of certain therapeutic drugs known to change plasma NE levels by determining drug-induced NE pharmacokinetic changes. Identifying conditions in which NE pharmacokinetics are defective and drugs which affect these processes will promote more effective pharmacotherapy. 5) We will determine if heightened SNS activity is associated with greater anxiety or depression in normal subjects or in patient subgroups, particularly young borderline hypertensive subjects.
| Lake, C R (1991) Manic psychosis after coffee and phenylpropanolamine. Biol Psychiatry 30:401-4 |
| Lake, C R; Gallant, S; Masson, E et al. (1990) Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 89:195-208 |
| Lake, C R; Rosenberg, D B; Gallant, S et al. (1990) Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 47:675-85 |
| Lake, C R; Rosenberg, D; Quirk, R (1990) Phenylpropanolamine and caffeine use among diet center clients. Int J Obes 14:575-82 |
| Lake, C R; Zaloga, G; Bray, J et al. (1989) Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine: a placebo-controlled follow-up study. Am J Med 86:427-32 |
