Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats.

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY.

Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in rats.

Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, . pre-hypertensive (SHR7) and with established hypertension (SHR16).

Clopidogrel Partially Counteracts Adenosine-5'-Diphosphate Effects on Blood Pressure and Renal Hemodynamics and Excretion in Rats.

Background: Adenosine-5'-diphosphate (ADP) can influence intrarenal vascular tone and tubular transport, partly through activation of purine P2Y12 receptors (P2Y12-R), but their actual in vivo role in regulation of renal circulation and excretion remains unclear.

Methods: The effects of intravenous ADP infusions of 2-8mg/kg/hour were examined in anesthetized Wistar rats that were untreated or chronically pretreated with clopidogrel, 20mg/kg/24hours, a selective P2Y12-R antagonist. Renal blood flow (transonic probe) and perfusion of the superficial cortex and medulla (laser-Doppler fluxes) were measured, together with urine osmolality (U), diuresis (V), total solute (UV), sodium (UV) and potassium (UV) excretion.

Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensin II, renal haemodynamics and renal excretion in two models of hypertension in the rat.

What is the central question of this study? We examined, in hypertensive rats, whether the angiotensin-converting enzyme-independent enzymes generating angiotensin II in the tissues modulate blood pressure, peripheral circulation and renal function. What is the main finding and its importance? The results suggest that chymostatin-sensitive enzymes diminish vascular tone in renal and extrarenal vascular beds. Chymase or similar chymostatin-sensitive enzymes have a significant role in the synthesis of angiotensin II in different tissues but do not control blood pressure in the short term, similarly in salt-dependent or Goldblatt-type rat hypertension.

Effects of liposomes with polyisoprenoids, potential drug carriers, on the cardiovascular and excretory system in rats.

Background: The unpredictable side effects of a majority currently used drugs are the substantial issue, in which patients and physicians are forced to deal with. Augmenting the therapeutic efficacy of drugs may prove more fruitful than searching for the new ones. Since recent studies show that new cationic derivatives of polyisoprenoid alcohols (APrens) might exhibit augmenting properties, we intend to use them as a component of liposomal drug carriers.