In a canine model of hypertension, α1-adrenergic blockade with prazosin restored muscle metaboreflex-induced increases in coronary blood flow and ventricular contractility to normotensive levels.
Does alpha-1-adrenergic blockade restore muscle metaboreflex-induced increases in coronary blood flow and ventricular performance in a canine model of hypertension?
In a canine model of hypertension, exaggerated sympathetic nerve activity causes coronary vasoconstriction that limits oxygen delivery and ventricular performance during exercise, which can be restored by alpha-1-adrenergic blockade.
Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α 1 -adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/d t max , and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α 1 -adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN. NEW & NOTEWORTHY We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α 1 -Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/metaboreflex-induced-functional-coronary-vasoconstriction/ .
Spranger et al. (Sat,) conducted a other in Hypertension. α1-adrenergic blockade (prazosin) vs. Hypertension without blockade was evaluated on Changes in coronary blood flow, left ventricular dP/dt max, and cardiac output. In a canine model of hypertension, α1-adrenergic blockade with prazosin restored muscle metaboreflex-induced increases in coronary blood flow and ventricular contractility to normotensive levels.