The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. ...

We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [3H]norepinephrine elicited by nerve stimulation (2 Hz, 0.5 millisecond, for 2 minutes) in rat atria isolated with their cardioaccelerans nerves. The stimulation-induced release of [3H]norepinephrine was increased 50% by 3 x 10(-8) mol/L of either peptide. No further increase in [3H]norepinephrine release was obs...

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. ...

Substantial progress has been made recently in the development of nonpeptide angiotensin II receptor antagonists, a goal that has long remained an unmet challenge. Pieter Timmermans and colleagues review the pharmacology and the course of events that led to the identification of the lead compound and clinical candidate DuP753. Nonpeptide angiotensin II receptor antagonists represent novel thera...

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...

Diabetic nephropathy (DN) is one of the major causes of end stage renal disease. Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) are preferred for delaying progression of DN. This study compared the preventive renal effects of telmisartan (10 mg/kg, p.o.), an ARB that completely blocks angiotensin action, and benazepril (5 mg/kg, p.o.), an ACE inhibitor, whi...

Angiotensin II and endothelin-1 activate their respective AT(1) and ET(A) receptors on vascular smooth muscle cells, producing vasoconstriction, and both peptides are implicated in the pathogenesis of essential hypertension. Angiotensin II potentiates the production of endothelin, and conversely endothelin augments the synthesis of angiotensin II. Both AT(1) and ET(A) receptor antagonists lower...

This review article looks at the emerging concepts about the renin angiotensin system. The specific aspects it covers include angiotensin II receptors, angiotensin receptor antagonists and alternative enzymatic pathways for the conversion of angiotensin I to angiotensin II other than angiotensin converting enzyme. The review, additionally, looks at the current and future clinical applications o...

We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II. Afferent arterioles were diss...