spontaneously. hypertensive

Hexamethonium Bromide (Hexamethonium Dibromide), a specific antagonist of neuronal-type nicotinic AChR in ganglia, is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier.

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.

Phenidone (1-phenyl-3-pyrazolidinone) is a dual inhibitor of cyclooxygenases and lipoxygenases that ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes[1]. The lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat[2].

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

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

Urocortin II, a neuropeptide hormone within the corticotropin-releasing factor (CRF) family—which comprises mammalian CRF, urocortin I, urocortin III, frog sauvagine, and piscine urotensin I—displays 34, 43, and 37-40% sequence homology with rat and human CRF, human urocortin I, and human urocortin III, respectively. This compound enhances rabbit ventricular myocyte shortening and relaxation in both a time- and concentration-dependent manner. In vivo studies reveal that urocortin II lowers arterial blood pressure in both normotensive and spontaneously hypertensive rats through peripheral CRF2 receptor agonism, inducing dose-dependent tachycardia and hypotension at doses of 3 and 30 pmol/kg. Additionally, it mitigates the visceral pain response to colorectal distension at 10 and 20 μg/kg in conscious rats and delays gastric emptying in mice.

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

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)

Quinapril-d5 is intended for use as an internal standard for the quantification of quinapril by GC- or LC-MS. Quinapril is a prodrug form of the angiotensin converting enzyme (ACE) inhibitor quinaprilat. In vivo, quinapril reduces mean arterial pressure in renal hypertensive and spontaneously hypertensive rats. It inhibits angiotensin I-induced pressor responses in normotensive rats and dogs. Quinapril prevents left ventricular heart failure in CHF 14.6 cardiomyopathic hamsters. Formulations containing quinapril have been used in the treatment of hypertension, heart failure, and diabetic nephropathy.

BAY-747 (BAY 1165747) is an orally administered, brain-penetrant compound that stimulates soluble guanylate cyclase (sGC). It effectively counteracts memory impairments induced by L-NAME, improves cognitive performance in rats during the object location task (OLT), reduces blood pressure in conscious normotensive and spontaneously hypertensive rats (SHR), and enhances skeletal muscle function in the mdx mTRG2 mouse model of Duchenne muscular dystrophy (DMD) [1] [2] [3].

3alpha-Dihydrocadambine exhibits dose-dependent hypotensive and anti-hypertensive effects in anesthetized normotensive rats and in conscious spontaneously hypertensive rats.

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.

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

(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..

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.

R 715, a bradykinin B1 receptor antagonist, inhibits contractions in isolated human umbilical cords that express bradykinin B1 receptors (pA2 = 8.49). When administered at doses of 200, 400, and 600 µg/kg, R 715 enhances latency to tail withdrawal in the tail-flick test for diabetic neuropathy mouse models induced by streptozotocin (STZ), signaling potential analgesic properties. Furthermore, at a 1 mg/kg per day dosage, it mitigates symptoms in a mouse model of experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 antigen peptide, such as reducing hind limb weakness and paralysis, improving gait symmetry, and decreasing spinal inflammation, neuron demyelination, and lesion monocyte invasion. Additionally, R 715 at 0.01 nmol/animal, administered intracerebroventricularly (i.c.v.), lowers mean arterial blood pressure and increases heart rate in spontaneously hypertensive rats, indicating cardiovascular effects.

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).

HS56 is an ATP-competitive dual Pim DAPK3 inhibitor, displaying K_i values of 0.26 μM for DAPK3, 0.208 μM for Pim-3, 2.94 μM for Pim-1, and >100 μM for Pim-2. This compound effectively inhibits LC20 phosphorylation and smooth muscle contraction, and reduces blood pressure in spontaneously hypertensive mice, making it a valuable tool for hypertension research [HS-56].

Antihypertensive agent 3 (compound 4a), an angiotensin II receptor 1 antagonist, demonstrates antihypertensive activity in spontaneously hypertensive rats (SHRs) [1].

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.

Theobromine-d6 is intended for use as an internal standard for the quantification of theobromine by GC- or LC-MS. Theobromine is a methylxanthine alkaloid and derivative of caffeine that has been found in cocoa beans and has diverse biological activities. It is an adenosine A1 receptor antagonist. Theobromine increases AMPK phosphorylation and inhibits adipocyte differentiation, ERK and JNK phosphorylation, and IL-6 and TNF-α production in 3T3-L1 preadipocytes cultured in differentiation medium. It inhibits decreases in renal cortex SIRT1 activity and increases in NADPH oxidase-dependent reactive oxygen species (ROS) production, as well as reduces kidney hypertrophy and albuminuria in a spontaneously hypertensive rat model of streptozotocin-induced diabetes when administered at a dose of 5 mg/kg per day.3 Theobromine is toxic to dogs with an LD50 value of 250 to 500 mg/kg.

Moexipril-d5 intended for use as an internal standard for the quantification of moexipril by GC- or LC-MS. Moexipril is a prodrug form of the angiotensin converting enzyme (ACE) inhibitor moexiprilat. It is converted to moexiprilat in vivo by side chain ester hydrolysis. Moexipril inhibits ACE in a cell-free assay (IC50 = 2.7 µM for the rabbit enzyme). It also inhibits phosphodiesterase 4 (IC50s = 38, 160, and 230 µM for PDE4B2, PDE4A5 and PDE4D5, respectively). Moexipril (0.1-30 mg/kg per day) reduces blood pressure in spontaneously hypertensive rats.1 It also reduces infarct volume in a rat model of focal cerebral ischemia when used at a concentration of 0.01 mg/kg.