Sympathetic Control of Coronary Circulation During Cold Pressor Test

Abstract

Coronary circulation is tightly regulated by several redundant mechanisms matched to the myocardial metabolic demand, which is directly related to myocardial mechanical work. However, our knowledge about the integrated autonomic control of coronary circulation during stress in humans is incomplete. The cold pressor test (CPT) has been used to evaluate the effect of centrally mediated increases in sympathetic activation. This noxious reflex evokes the increase of vascular resistance (VR), blood pressure (BP) and cardiac work. However, the effect of the sympathetic control on coronary circulation during a sympathetic mediated reflex is unknown. Therefore, we aimed to test the effect of the β-adrenergic receptor (AR) and α-AR on coronary circulation in humans during CPT. In 19 men (27±1 years; 23±1 kg‧m-2; mean±SE) and 13 women (24±1 years; 24±1 kg‧m-2; mean±SE), we measured heart rate (HR), BP, cardiac output (CO), total (TVR) and coronary blood peak velocity (CBV). Coronary conductance index (CCI: CBV/diastolic BP) and the estimated myocardial oxygen consumption (MVO2: 7.2 × 10-4 (Systolic BP × HR) + 1.43)were calculated; at rest and during CPT, before and after an oral administration a β-AR blocker (propranolol; men: 1.6±0.1mg‧kg-1 and women: 1.7±0.1mg‧kg-1), and a α-AR blocker (prazosin; men: 0.038±0 mg‧kg-1 and women: 0.039±0 mg‧kg-1), in two laboratory visits. On the control session, CPT did not change HR, increased mean arterial pressure (MAP), CO and TVR only in men. Also, CPT increased the MVO2, CBV and decreased CCI. The β-AR blockade decreased HR and did not change BP at rest. CPT did not change HR (men: -1±2 bpm; women:1±1 bpm), and increased MAP (men: 26±10 mmHg; women: 21±11 mmHg). CO decreased at rest after the β-AR blockade while maintaining the response to CPT (men: 0.4±0.2 l‧min-1; women: 1.0±0.1 l‧min-1). The β-AR blockade increased TVR at rest, but did not change the response to CPT (men: 3±1 mmHg‧l‧min-1; women: -1±0.4 mmHg‧l‧min-1). The β-AR blockade reduced MVO2 and blunted its response to CPT (men: 2.3±0.3 a.u.; women: 2.1±0.3 a.u.); however abolishing the increase of CBV, then not changing the CCI response to CPT (men: -0.15±0.02 cm‧s-1‧mmHg-1; women: -0.13±0.02 cm‧s-1‧mmHg-1). The α-AR blockade increased HR at rest, not changing the response to CPT (men: 3±3bpm; women: 4±3 bpm). There was no effect of the α-AR blockade on BP at rest; however, blunted its response to CPT (MAP - men: 20±4 mmHg; women: 8±3 mmHg). The α-AR blockade did not change CO, which increased during CPT (men: 0.66 ±0.21 l‧min-1; women: 1.10±0.21 l‧min-1). The α-AR blockade did not change TVR, and prevented its increase during CPT. The estimated MVO2 did not change after the α-AR blockade, and increased during CPT (men: 2.0±0.4 a.u.; women: 1.4±0.5 a.u.). The α-AR blockade did not change CBVat rest or the response to CPT (men: 3.1±1.4 cm‧s-1; women: 5.4± 3.6 cm‧s-1), as well as, did not change the CCI at rest or the response to CPT. Ultimately, no sex differences were observed. The β-AR vasodilation plays a key role to the increase of the coronary circulation during sympathetic activation. Additionally, it seems that the α-AR exerts no effect on coronary circulation during sympathetic activation in humans.