High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociation constant of 3.1 mM. The binding inhibition activities of analogues of angi...

Angiotensin II elicits a receptor-mediated positive inotropic response in cardiac tissue from most mammalian species by activating voltage-sensitive slow Ca2+ channels. In the guinea pig, we confirm there is no in vitro contractile force development in bioassay systems using isolated hearts or left atrial tissue in response to angiotensin peptides. However, 125I-angiotensin II binding sites tha...

Recent studies suggest that angiotensin II is released from neuronal tissue in vitro, but the occurrence of this phenomenon in the intact brain has not yet been demonstrated. To characterize the in vivo release of immunoreactive angiotensin II, push-pull cannulas were positioned in the anterior hypothalamus in 47 Sprague-Dawley rats (200-250 g) anesthetized with Inactin (100 mg/kg i.p.). Artifi...

We previously reported the generation of transgenic mice containing the entire human renin gene with a 900-bp promoter. To determine whether all the required elements for angiotensin II-mediated suppression of human renin are present in these mice, angiotensin II was chronically infused by means of osmotic minipump at both low and high doses, 200 and 1000 ng/kg per minute, respectively. Blood p...

Angiotensin II induces endothelial dysfunction by reducing NO availability and increasing reactive oxygen species. We assessed whether cyclooxygenase (COX)-1 or COX-2 participate in the angiotensin II–induced endothelial dysfunction in murine mesenteric small arteries and examined the role of reduced nicotinamide-adenine dinucleotide phosphate–dependent reactive oxygen species production. Mice ...

The rostral and caudal parts of the ventrolateral medulla play a major role in the control of blood pressure. Both regions contain a high density of receptor binding sites for angiotensin II, and it has been shown previously that microinjection of angiotensin II into the rostral ventrolateral medulla causes a rise in blood pressure. The aims of this study were to determine the cardiovascular ef...

Activation of the Na+/H+ exchanger isoform-1 (NHE-1) by angiotensin II is an early signal transduction event that may regulate vascular smooth muscle cell (VSMC) growth and migration. Many signal transduction events stimulated by angiotensin II are mediated by the mitogen-activated protein (MAP) kinases. To define their roles in angiotensin II-mediated NHE-1 activity, VSMCs were treated with an...

Chronic intravenous infusion of subpressor doses of angiotensin II causes blood pressure to increase progressively over the course of several days. The mechanisms underlying this response, however, are poorly understood. Because high-dose angiotensin II increases oxidative stress, and some compounds that result from the increased oxidative stress (eg, isoprostanes) produce vasoconstriction and ...

Recent evidence indicates that inflammation plays a critical role in the initiation and progression of hypertensive kidney disease. However, the signaling mechanisms underlying the induction of inflammation are poorly understood. We found that chemokine (C-X-C motif) ligand 16 (CXCL16) was induced in renal tubular epithelial cells in response to angiotensin II in a nuclear factor-κB-dependent m...

Experiments were performed to determine whether exogenous L-arginine could ameliorate angiotensin II-induced hypertension and renal damage. Rats were instrumented with chronic indwelling femoral venous and arterial catheters for infusions of drugs and measurement of conscious arterial pressure. Arterial blood pressure significantly increased from 124+/-1 to 199+/-4 mm Hg, after 9 days of contin...