Decreased susceptibility to salt-induced hypertension in subtotally nephrectomized mice lacking the vasopressin V1a receptor.

Aims: By examining vasopressin V1a receptor (V1aR) knockout (KO) mice, we previously found that the V1aR is critically involved in the regulation of normal blood pressure. The present study was undertaken to elucidate the role of the V1aR in salt-induced hypertension.

Methods And Results: We compared haemodynamic responses induced by subtotal nephrectomy + salt loading in V1aR KO mice with those of wild-type (WT) controls.

Vasopressin V1A receptor enhances baroreflex via the central component of the reflex arc.

The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts its physiological actions via 3 distinct receptor isoforms designated V1A, V1B, and V2. We recently showed that V1A receptor was involved in the baroreflex control of heart rate using V1A receptor knockout mice. The present study was undertaken to further clarify this finding.

V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity.

Arginine-vasopressin (AVP) is a hormone that is essential for both osmotic and cardiovascular homeostasis, and exerts important physiological regulation through three distinct receptors, V1a, V1b, and V2. Although AVP is used clinically as a potent vasoconstrictor (V1a receptor-mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined. In this study, we investigated the functional roles of the V1a receptor in cardiovascular homeostasis using gene targeting.

Preferable anesthetic conditions for echocardiographic determination of murine cardiac function.

Ketamine and xylazine are routinely used for measurement of hemodynamics of mice and rats by echocardiography. The anesthetic agents produce low heart rate (HR) in the animals, which may result in misleading data in the hemodynamic profiles of the small animals. The purpose of the present study was to select an appropriate anesthetic condition in the evaluation of mouse and rat cardiac function by echocardiography.

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram.

Direct inhibition of neutral endopeptidase in vasopeptidase inhibitor-mediated amelioration of cardiac remodeling in rats with chronic heart failure.

Vasopeptidase inhibitors possess dual inhibitory actions on neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) and have beneficial effects on cardiac remodeling. However, the contribution of NEP inhibition to their effects is not yet fully understood. To address the role of cardiac NEP inhibition in the anti-remodeling effects of a vasopeptidase inhibitor, we examined the effects of omapatrilat on the development of cardiac remodeling in rats with left coronary artery ligation (CAL) and those on collagen synthesis in cultured fibroblast cells.

Insights into alpha1 adrenoceptor function in health and disease from transgenic animal studies.

Alpha(1)-adrenoceptors (ARs) mediate some of the main actions of the natural catecholamines, epinephrine and norepinephrine, and have a crucial role in the regulation of arterial blood pressure. Since alpha(1)-AR was subdivided into three subtypes (alpha(1A)-AR, alpha(1B)-AR and alpha(1D)-AR), the search has been on to discover subtype-specific physiological roles and to develop subtype-selective agonists and antagonists. Recently, several strains of genetically engineered mice have become available.

Beneficial effects of sampatrilat, a novel vasopeptidase inhibitor, on cardiac remodeling and function of rats with chronic heart failure following left coronary artery ligation.

Sampatrilat is a novel vasopeptidase inhibitor that may offer a greater benefit than traditional angiotensin-converting enzyme (ACE) inhibitors in the treatment of chronic heart failure (CHF). The present study was undertaken to determine whether sampatrilat improves hemodynamic function and cardiac remodeling through a direct action on the failing heart in rats with CHF following left coronary artery ligation (CAL). Sampatrilat (30 mg/kg a day) was administered orally to the animals from the 1st to 6th week after the operation.

The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction.

To investigate the physiological role of the alpha(1D)-adrenergic receptor (alpha(1D)-AR) subtype, we created mice lacking the alpha(1D)-AR (alpha(1D)(-/-)) by gene targeting and characterized their cardiovascular function. In alpha(1D)-/- mice, the RT-PCR did not detect any transcript of the alpha(1D)-AR in any tissue examined, and there was no apparent upregulation of other alpha(1)-AR subtypes. Radioligand binding studies showed that alpha(1)-AR binding capacity in the aorta was lost, while that in the heart was unaltered in alpha(1D)-/- mice.