Activation of the 5‐HT7 receptor but not nitric oxide synthase is necessary for chronic 5‐hydroxytryptamine‐induced hypotension. Issue 12 (22nd October 2020)

• Record Type: Journal Article
• Authors: Seitz, Bridget M.; Fink, Gregory D.; Watts, Stephanie W.
• Is Part Of: Experimental physiology. Volume 105:Issue 12(2020:Dec.)
• Page Start: 2025
• Page End: 2032
• Publication Date: 2020-10-22
• Subjects: 5‐HT -- 5‐HT7 receptor -- hypotension -- nitric oxide synthase; Physiology, Experimental -- Periodicals; 571.0724
• DOI: 10.1113/EP088919
• Languages: English
• ISSNs: 0958-0670

Abstract

Abstract : New Findings: What is the central question of this study? What mechanisms account for the hypotension observed during chronic elevations in circulating 5‐hydroxytryptamine in rats? What is the main finding and its importance? Chronic 5‐hydroxytryptamine‐induced hypotension requires continued activation of the 5‐HT7 receptor subtype but does not require NO, an outcome that resolves previous conflicting results. Therapeutic interruption of the hypotensive actions of 5‐HT under pathophysiological conditions can only be achieved through blockade of the 5‐HT7 receptor. Abstract: Low dose infusion of 5‐hydroxytryptamine (5‐HT) to rats causes both an acute and a chronic fall in arterial blood pressure. The 5‐HT7 receptor subtype plays a critical part in the observed hypotension. Acute (minutes to hours) 5‐HT infusion shows no depressor role for nitric oxide (NO), but 5‐HT depressor responses under chronic conditions suggest that NO production may be critical. We test the hypothesis that NO contributes to the chronic, but not the acute, depressor response to 5‐HT. We compared the role of NO and 5‐HT7 receptors in 5‐HT‐induced hypotension under acute and chronic conditions in the same animal. Mean arterial pressure and heart rate were measured by radiotelemetry in conscious rats during 5 days of saline or 5‐HT (25 μg kg −1 min −1 ; osmotic pump) infusion and for 2 days after infusion was stopped. To quantify the contributions of NO and the 5‐HT7 receptor to 5‐HT‐induced hypotension, the nitric oxide synthase (NOS) inhibitor l ‐NAME or the selective 5‐HT7 receptor antagonist SB‐267790 were given at 1, 3 and 5 days of chronic infusion, and 1 day after 5‐HT infusion pumps were removed. N ω ‐Nitro‐l ‐arginine methyl ester (l‐NAME) caused a pressor response of the same magnitude in the absence or presence of 5‐HT infusion. Conversely, SB‐269970 did not affect mean arterial pressure in the absence of 5‐HT infusion and reversed the 5‐HT‐induced depressor response at each time point. Our findings demonstrate that acute and chronic 5‐HT‐induced hypotension does not require NOS activation but does require continued activation of the 5‐HT7 receptor. Abstract :