The Enhancement of a Serotonin-Mediated Reduction in Blood Pressure by a Diuretic: An Effective Anti-Hypertensive Combination

Serotonin (5-hydroxytryptamine, 5-HT) causes a sustained reduction in mean arterial pressure (MAP) during chronic (one week) infusion in both normo- and hypertensive rats. We hypothesized that the administration of a diuretic would enhance the hypotensive effect of 5-HT. Male Dahl-SS rats on normal diet were instrumented with radio telemeters for blood pressure measurement. Following the collection of baseline MAP Alzet mini-pumps containing 5-HT (25 ug/kg/min) were implanted. On the same day as pump implantation rats were either: 1) switched to drinking water containing the diuretic trichlormethiazide (TCM- 250 mg/L) or 2) maintained on regular drinking water. Following a week of infusion blood samples were collected and IDEXX blood chemistry panels were run to investigate any potential effects on liver, kidney, or cardiometabolic parameters as well as electrolyte balance. After 1 week of infusion rats receiving both 5-HT and TCM had a significantly lower MAP (122 ± 3.3 mmHg; n=5) than rats receiving either 5-HT or TCM alone. (131± 2.7 mmHg; n=5, 127 ± 3.5 mmHg; n=4). There was no effect of 5-HT administration on kidney or liver function as assessed by blood serum measurements of creatinine, blood urea nitrogen (BUN), albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALKP), and total bilirubin (see table). Collectively, these data suggest 5-HT works as a safe, effective anti-hypertensive treatment alongside current front-line anti-hypertensive medications. [Table: see text] NIH HL151413 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.