Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1 microM and 10 microM) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10 microM), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged. Systemic injections with 5-HT1A agonist, buspirone (1.0-5.0 mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in the dorsal raphé and in the hippocampus. The decreases in the raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.0 mM (-) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (-) pindolol alone (0.01-1.0 mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100 nM), or produced a small increase (1.0 mM) in raphé 5-HT, without changing hippocampal 5-HT. These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT1A receptors control somatodendritic and hippocampal 5-HT release

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is associated with higher rates of cardiovascular, metabolic, and renal comorbidities as compared to equivalent primary hypertension (HTN). Objective: To evaluate the rates and patterns of PA screening across various at-risk populations. Methods: We performed a retrospective review of adult patients seen in a university-based outpatient setting between 1/1/17-6/30/20, who had HTN plus at least one of the following criteria: 1) taking ≥3 antihypertensive agents (resistant HTN); 2) age <35; 3) obstructive sleep apnea (OSA); 4) hypokalemia; or 5) an adrenal mass. We excluded patients with adrenal insufficiency, congenital adrenal hyperplasia, severe renal disease, and end stage heart failure. Results: We identified 93,362 patients (54.6% men, mean age 64±16 y, 82.3% white, 12.8% black, 2.3% Asian) meeting at least one PA screening criterion. Of these, 3.4% were screened for PA. Screening occurred in 2.7% (1,813/66,185) of patients with resistant HTN; 4.2% of those with HTN and OSA (1,297/29,322) or hypokalemia (599/5,387); 5.1% of those <35 y (461/8,573); and 46.5% (452/972) of patients with HTN and an adrenal mass. Multiple logistic regression showed that the odds of screening were highest in patients with hypokalemia: OR: 3.4 (3.2-3.7), and were independent of having atrial fibrillation or myocardial infarction. Among patients with resistant HTN and those with HTN and OSA, women vs. men (OR: 1.2-1.4) and blacks vs. all other races (OR: 2-2.6, p <0.0001 for all) were more likely to be screened. Conversely, among patients <35 y and those with adrenal masses, there were no race or sex differences. Although ~8 years younger, patients with resistant HTN and HTN+OSA screened had higher prevalence of chronic kidney disease, cerebrovascular accidents, dyslipidemia, and diabetes than those not screened. Conclusions: PA remains vastly under-recognized, even in large academic settings. Consideration for PA is given more often after comorbidities have developed. Enhancing awareness and screening rates for PA are critical for preventing cardio-renal and metabolic complications in many patients with HTN.