Table 4.

Compounds selected to challenge the CVS with the aim of distinguishing system- from drug-specific parameters and their mechanism of action

Compound	Class	MoA	Effect
Amiloride	Diuretic	Diuretics cause blood volume contraction and lower venous pressure, which decreases cardiac filling and, by the Frank-Starling mechanism, decreases ventricular SV (Levick, 2003).	SV
Amlodipine	Calcium channel blocker	Amlodipine is a dihydropyridine that blocks voltage gated calcium channels and selectively inhibits Ca2+ influx into vascular smooth muscle cells. Calcium antagonists act by decreasing TPR to lower arterial pressure. As a consequence, reflex tachycardia, increased CO, and increased plasma catecholamine and plasma renin activity are commonly seen, particularly with the initial dose and with short-acting dihydropyridines (Michalewicz and Messerli, 1997; Perez-Reyes et al., 2009).	TPR
Atropine	M2 receptor antagonist	Muscarinic (M2) receptor antagonist (MRA) is an agent that blocks the activity of the muscarinic acetylcholine receptor. It causes tachycardia by blocking vagal effects on the sinoatrial node. Acetylcholine hyperpolarizes the sinoatrial node which is overcome by MRA and thus increases the heart rate	HR
Enalapril	Angiotensin-converting enzyme (ACE) inhibitor	ACE inhibitors competitively inhibit angiotensin I-converting enzyme, preventing the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates release of aldosterone. Decreased levels of angiotensin II lead to decreased TPR that is unassociated with reflex stimulation of the heart (Frohlich, 1989). In addition, aldosterone acts on the distal tubules and collecting ducts of the nephron, the functional unit of the kidney. Decreased levels of aldosterone, cause the depletion of sodium, conservation of potassium, decreased water retention and decreased BP	TPR and SV
Fasudil	Rho-kinase inhibitor	Rho-kinase inhibits myosin light chain phosphatase activity and plays a key role in Ca2+ sensitization and hypercontraction of vascular smooth muscle cells. Rho-kinase inhibitors decrease TPR (Masumoto et al., 2001).	TPR
HCTZ	Diuretic	See amiloride	SV
Prazosin	Selective α1 adrenergic receptor blocker	Prazosin is a quinazoline derivative that is a specific and selective competitive antagonist of α1 adrenoceptors on vascular smooth muscle cells. Prazosin reduces BP by reducing elevated peripheral resistance and has little effect on cardiac function (Reid et al., 1987).	TPR
Propranolol	β-adrenergic receptor blocker	Propranolol is a non-selective beta blocker. It antagonizes the action of norepinephrine and epinephrine at all β-adrenergic receptors. Propranolol decreases CO and heart rate with a reflex rise in TPR (Ebadi, 2008).	HR