Coronary vasoconstrictor pathway from anterior hypothalamus includes neurons in RVLM.

We have previously identified discrete brain sites [anterior (AHA) and lateral hypothalamus, periaqueductal gray, pontine parabrachial nucleus, lateral reticular formation, and rostral ventrolateral medulla (RVLM)] in the cat, in which electrical or chemical activation produces coronary vasoconstriction. This study examines whether the most rostral (AHA) and caudal (RVLM) of these sites are connected as part of a common pathway mediating coronary vasoconstriction. In chloralose-anesthetized cats, electrical stimulation in the AHA produced maximum increases in arterial pressure (41 +/- 10%) and coronary vascular resistance (28 +/- 9%). Microinjection of lidocaine into the RVLM attenuated the increases in arterial pressure (10 +/- 3%) and coronary vascular resistance (5 +/- 1%) in response to electrical stimulation in the AHA (P < 0.05 vs. before lidocaine). Lidocaine nonspecifically inhibits neural elements in the region. gamma-Aminobutyric acid in the RVLM, which selectively inhibits cell bodies and not fibers passing through the RVLM, attenuated the increase in coronary vascular resistance (38 +/- 8 to 14 +/- 3%; P < 0.05) but not the increase in arterial pressure (87 +/- 12 to 92 +/- 16%) in response to electrical stimulation in the AHA. These data indicate that coronary vasoconstriction in response to electrical stimulation in the AHA requires cell bodies in the RVLM; however, the associated pressor response is mediated by fibers passing through the RVLM. We conclude that a polysynaptic descending pathway that mediates sympathetic coronary vasoconstriction descends from the AHA through a synaptic connection in the RVLM.

Inhibition of nitric oxide synthesis augments centrally induced sympathetic coronary vasoconstriction in cats.

The principal effect of sympathetic activation on the coronary circulation is an alpha-adrenergic coronary vasoconstriction in the presence of beta-receptor blockade. Secondary effects include vasodilation due to beta-adrenoceptor stimulation and alpha 2-mediated release of endothelium-derived relaxing factor (EDRF) from the coronary vascular endothelium. We hypothesized that blockade of nitric oxide synthesis (nitro-L-arginine methyl ester, L-NAME) would augment coronary vasoconstriction to sympathetic stimulation as a result of a decrease in alpha 2-mediated EDRF release. In chloralose-anesthetized cats, hypothalamic stimulation produced increases in coronary vascular resistance [maximum 26 +/- 9% (SE)] and arterial pressure (41 +/- 7%) and a decrease in coronary blood flow velocity (15 +/- 6%). L-NAME (3 mg/kg iv) increased baseline arterial pressure from 69 +/- to 92 +/- 7 mmHg (P < 0.05). After L-NAME, a greater increase in coronary vascular resistance (55 +/- 20%, P < 0.05), a decrease in coronary blood flow velocity (24 +/- 7%, P < 0.05), and a similar pressor response (34 +/- 7%) were observed in response to hypothalamic stimulation. L-Arginine reversed the effect of L-NAME on coronary vasoconstriction to hypothalamic stimulation. Similar increases in arterial pressure (from 73 +/- 3 to 91 +/- 5 mmHg, P < 0.05) with vasopressin (0.01-0.05 U/min) failed to enhance coronary vasoconstriction to activation in anterior hypothalamus. We conclude that inhibition of EDRF synthesis augments centrally induced sympathetic coronary vasoconstriction in the cat.