Quantitative assessment of the central versus peripheral effect of intravenous clonidine using baroreflex equilibrium diagrams

Abstract

Clonidine is a first-generation central antihypertensive that reduces sympathetic nerve activity (SNA). Although clonidine also exerts peripheral vasoconstriction, the extent to which this vasoconstriction offsets the centrally mediated arterial pressure (AP)-lowering effect remains unknown. In anesthetized rats (n = 8), we examined SNA and AP responses to stepwise changes in carotid sinus pressure under control conditions and after intravenous low-dose (2 μg/kg) and high-dose clonidine (5 μg/kg). In the baroreflex equilibrium diagram analysis, the operating-point AP under the control condition was 115.2 (108.5–127.7) mmHg [median (25th–75th percentile range)]. While the operating-point AP after low-dose clonidine was not significantly different with or without the peripheral effect, the operating-point AP after high-dose clonidine was higher with the peripheral effect than without [81.3 (76.2–98.2) mmHg vs. 70.7 (57.7–96.9), P < 0.05]. The vasoconstrictive effect of clonidine partly offset the centrally mediated AP-lowering effect after high-dose administration.

Acute effects of empagliflozin on open-loop baroreflex function and urine glucose excretion in Goto-Kakizaki diabetic rats

“…The neural effect of empagliflozin contrasts with that of clonidine, a central antihypertensive, examined in our previous study using the baroreceptor isolation procedure [ 25 ]. In that study, an intravenous administration of clonidine hydrochloride at 5 μg kg −1 (a cumulative dose of 7 μg kg −1 ) immediately suppressed SNA (the response range was narrowed from 93.9 ± 2.4 to 24.0 ± 6.2%, P < 0.001).…”

“…The neural effect of empagliflozin contrasts with that of clonidine, a central antihypertensive, examined in our previous study using the baroreceptor isolation procedure [25]. In that study, an intravenous A previous study demonstrated that a two-week treatment with dapagliflozin decreased the norepinephrine content in the kidneys in high-fat fed mice [26].…”

Acute effects of empagliflozin on open-loop baroreflex function and urinary glucose excretion in rats with chronic myocardial infarction

“…We employed an open-loop analysis of the carotid sinus baroreflex [ 20 ] because this method allows us to test the drug effect on SNA over a wide range of carotid sinus pressure (CSP). For instance, the sympathoinhibitory effect of a central antihypertensive, clonidine, is more evident in the low CSP (high SNA) range than in the high CSP (low SNA) range [ 21 ]. Generally speaking, heart failure causes renal hypoperfusion and induces potential tubular damages [ 22 , 23 ].…”

Dexmedetomidine Attenuates Lipopolysaccharide-Induced Sympathetic Activation and Sepsis via Suppressing Superoxide Signaling in Paraventricular Nucleus

“…Sympathetic outflow is mainly regulated by activation of the presynaptic α2A subtype, which is the predominant α2R subtype in the brain and exerts an inhibitory role in sympathetic activity [ 20 ]. α2R agonist clonidine serves as the first-generation central antihypertensive drug that reduces sympathetic outflow [ 21 ].…”