hypertensive rats

CGP48369 is a potent angiotensin II receptor antagonist with antihypertensive effects that enhances endothelium-dependent relaxation of coronary arteries in spontaneously hypertensive rats.

ME-3221 is an angiotensin AT1 receptor antagonist that prevents hypertensive complications in aged stroke-prone hypertensive rats.

N,N'-Dicyclohexylurea (AURORA KA-3582) is a soluble epoxide hydrolase (sEH) inhibitor.

Tempone is an aminooxyalkane that acts as a free radical scavenger and reacts with reactive oxygen species (ROS). Intravenous Tempone reduces mean arterial pressure in spontaneously hypertensive rats.

Nitroflurbiprofen (Nitroxybutyl flurbiprofen) is a NO-releasing COX inhibitor and modulates the increased intrahepatic vascular tone in portal hypertensive cirrhotic rats.

(4E)-SUN9221 is a potent dual α1-adrenergic receptor and 5-HT2 receptor antagonist, exhibiting antihypertensive and antiplatelet aggregation activities in hypertensive rats.

AVE3085 is an endothelial nitric oxide synthase enhancer that restores endothelial function and reduces blood pressure in spontaneously hypertensive rats, used in cardiovascular disease research.

Fasidotril is a NEP/ACE inhibitor. Fasidotril was an effective oral antihypertensive agent during chronic treatment in high-renin renovascular rats, normal-renin SHR, and low-renin DOCA-salt hypertensive rats and in patients with essential hypertension.

KRH-594 is a potent, specific and insurmountable AT1 receptor antagonist. KRH-594 ameliorates hyperlipidaemia and nephropathy in diabetic spontaneously hypertensive rats. KRH-594 prevents end-organ damage in stroke-prone spontaneously hypertensive Izm ra

Milfasartan is a potent, selective antagonist of AT1 receptor with oral activity. It markedly lowers the blood-pressure in conscious renal and spontaneously hypertensive rats.

Firibastat (RB150) is a glutamyl aminopeptidase antagonist and an orally active brain penetrating prodrug of EC33. It is a first-in-class brain aminopeptidase A (APA) inhibitor with a Ki of 200 nM. Firibastat selectively and specifically inhibits conversion of brain angiotensin-II into angiotensin-III and decreases blood pressure in hypertensive rats[1][2].

BMY 7378 dihydrochloride (BMY7378 HCl) , α1D-adrenergic receptor antagonist, is a weak partial agonist antagonist of 5-HT1A receptor.

RO 46-8443 is the first non-peptide endothelin ETB receptor selective antagonist. RO 46-8443 displays up to 2000-fold selectivity for ETB receptors both in terms of binding inhibitory potency and functional inhibition.

Guanfacine-13C,15N3is intended for us as an internal standard for the quantification of guanfacine by GC- or LC-MS. Guanfacine is an α2-adrenergic receptor (α2-AR) agonist with Kivalues of 93, 1,380, and 3,890 nM for α2A-, α2B-, and α2C-ARs, respectively, in a radioligand binding assay.1It has EC50values of 52, 288, and 602 nM for α2A-, α2B-, and α2C-ARs, respectively, for stimulated [35S]GTPγS binding. It also binds to imidazoline receptor 1 (Ki= 19 nM in a radioligand binding assay).2Guanfacine (0.3-5 mg/kg) binds to adrenergic receptors in the central nervous system and lowers blood pressure in hypertensive rats in a dose-dependent manner.3It also improves spatial working memory deficits induced by hypobaric hypoxia in rats.4Formulations containing guanfacine are used in the treatment of high blood pressure and attention deficit hyperactivity disorder (ADHD). 1.Jasper, J.R., Lesnick, J.D., Chang, L.K., et al.Ligand efficacy and potency at recombinant α2 adrenergic receptors: Agonist-mediated [35S]GTPγS bindingBiochem. Pharmacol.55(7)1035-1043(1998) 2.Nikolic, K., Filipic, S., and Agbaba, D.QSAR study of imidazoline antihypertensive drugsBioorg. Med. Chem.16(15)7134-7140(2008) 3.Scholtysik, G.Pharmacology of guanfacineBr. J. Clin. Pharmacol.10(Suppl 1)21S-24S(1980) 4.Kauser, H., Sahu, S., Kumar, S., et al.Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive declineNeuroscience254110-119(2013)

Chlorthalidone impurity G is a potential impurity found in commercial preparations of chlorthalidone that has moderate antihypertensive effects. Chlorthalidone is a thiazide-like diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, which prevents reabsorption of sodium and chloride leading to a reduction in plasma volume and cardiac output. It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (Kis = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (Kis = 138-1,347 nM), which may mediate its sustained vasodilatory activity. Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy induced by deoxycorticosterone acetate (DOCA) in salt-hypertensive rats. Formulations containing chlorthalidone have been used alone or in combination with other antihypertensive agents to lower arterial blood pressure and as adjuvants to address edema caused by cardiac or renal disorders.

Methylspinazarin is a naphthoquinone bacterial metabolite that has been found in Streptomyces and is an inhibitor of catechol O-methyltransferase (COMT; IC50 = 0.8 μg ml).1 It is selective for COMT over tyrosine hydroxylase, DOPA decarboxylase, and dopamine-β-hydroxylase at 100 μg ml. Methylspinazarin decreases blood pressure in spontaneously hypertensive rats when administered at a dose of 50 mg kg. |1. Chimura, H., Sawa, T., Takita, T., et al. Methylspinazarin and dihydromethylspinazarin, gatechol-O-methyl transerfase inhibitors produced by Streptomyces. J. Antibiot. 26(2), 112-114 (1973).

Adrenomedullin (13-52) is a truncated form of adrenomedullin (1-52) . It induces nitric oxide-dependent relaxation of and inhibits release of angiotensin II and endothelin-1 from isolated rat aorta. In vivo, adrenomedullin (13-52) decreases mean arterial pressure (MAP) in spontaneously and renal hypertensive rats in a dose-dependent manner. Adrenomedullin (13-52) (10-3,000 ng per animal) reverses increases in lobar arterial pressure induced by U-46619 in a dose-dependent manner in cats but has no effect on basal lobar arterial pressure or systemic arterial pressure. It also potentiates inflammatory edema and neutrophil accumulation in rats.

Potent EGFR-kinase inhibitor (IC50 = 0.7 nM). Displays >3000-fold selectivity against a panel of serine/threonine kinases. Reduces metastasis and angiogenesis in a mouse model of pancreatic cancer. Antihypertensive and orally bioavailable. Bruns et al (2000) Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 60 2926 PMID:10850439 |Ulu et al (2013) Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats. J.Pharmacol.Exp.Ther. 345 393 PMID:23528611 |Kaspersen et al (2012) Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena. Bioorg.Chem. 44 35 PMID:22832269

Deacetylforskolin is a diterpene and a derivative of forskolin that has been found inC. forskohliiand has diverse biological activities.1,2,3,4It activates rat adipocyte adenylyl cyclase (IC50= 20 μM) and inhibits glucose transport in rat adipocyte plasma membranes.2Deactylforskolin (30-1,000 μg/kg) reduces blood pressure in spontaneously hypertensive rats.3It also attenuates hypercapnia-induced impairments in the passive avoidance response in mice.4 1.Gabetta, B., Zini, G., and Danieli, B.Minor Diterpenoids of Coleus forskohliiPhytochemistry28(3)859-862(1989) 2.Joost, H.G., Habberfield, A.D., Simpson, I.A., et al.Activation of adenylate cyclase and inhibition of glucose transport in rat adipocytes by forskolin analogues: structural determinants for distinct sites of actionMol. Pharmacol.33(4)449-453(1988) 3.Bhat, S.V., Dohadwalla, A.N., Bajwa, B.S., et al.The antihypertensive and positive inotropic diterpene forskolin: Effects of structural modifications on its activityJ. Med. Chem.26(4)486-492(1983) 4.McCulloch, A.J., Thomson, T.A., and Deacon, R.Hypoxic amnesia and its reversal with forskolinBiochem. Soc. Trans.17(1)212-213(1988)

Alamandine can be formed from angiotensin A by action of ACE-2 or directly from angiotensin-(1-7) by decarboxylation of its aspartate residue. The angiotensin A analog produces effects resembling those of Ang II (1-7). However, it acts independently of the two known vasodilators receptors of the RAS (Mas and angiotensin II type 2). To produce its effects, alamandine binds to the Mas-related receptor, MrgD. A novel orally active formulation of alamandine produced a long-term antihypertensive effect in spontaneously hypertensive rats and cardioprotective effects. These novel findings will be helpful for developing a new understanding of the RAS, a key regulator of blood pressure and fluid balance. The heptapeptide could serve as a model peptide, e.g. in the development and evaluation of analytical methods.

(R)-Fadrozole ((R)-CGS 16949A; FAD286) is a potent nonsteroidal inhibitor. (R)-Fadrozole also inhibits human placental aromatase (pIC 50 = 6.17) and aldosterone biosynthesis. (R)-Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats..

Trandolapril is an orally administered angiotensin converting enzyme (ACE) inhibitor that is hydrolysed to the active diacid trandolaprilat.

EP3 antagonist 3, a potent and selective EP3 antagonist with the advantage of oral activity, significantly inhibited GR63799- or acetic acid-induced reduction in bladder capacity and PGE2-induced overactive bladder model in spontaneously hypertensive rats (SHR).

Benidipine is a potent, orally active calcium channel antagonist. benidipine increases endothelial nitric oxide synthase activity and improves coronary circulation in hypertensive rats. benidipine resists apoptosis in ischemic reperfused cardiomyocytes.