1. Effects of Black Garlic Extract and Nanoemulsion on the Deoxy Corticosterone Acetate-Salt Induced Hypertension and Its Associated Mild Cognitive Impairment in Rats
Chun-Yu Chen, Tsung-Yu Tsai, Bing-Huei Chen Antioxidants (Basel). 2021 Oct 13;10(10):1611. doi: 10.3390/antiox10101611.
Organosulfur compounds, phenolic acids and flavonoids in raw and black garlic were determined, and followed by preparation of black garlic nanoemulsion for studying their effects on deoxycorticosterone acetate-salt-induced hypertension and associated mild cognitive impairment in rats. Three organosulfur compounds, including diallyl sulfide (87.8 μg/g), diallyl disulfide (203.9 μg/g) and diallyl trisulfide (282.6 μg/g) were detected in black garlic by GC-MS, while gallic acid (19.19 μg/g), p-coumaric acid (27.03 μg/g) and quercetin (22.77 μg/g) were detected by UPLC-MS/MS. High doses of both black garlic extract and nanoemulsion prepared using Tween-80, glycerol, grapeseed oil and water could decrease systolic blood pressure through the elevation of bradykinin and nitric oxide levels as well as diminish aldosterone and angiotensin II levels in rats. In Morris water maze test, they could significantly decrease escape latency and swimming distance and increase the time spent in the target quadrant, accompanied by a decline of acetylcholinesterase activity and malondialdehyde level in the hippocampus as well as a rise in glutathione level and activities of superoxide dismutase, catalase and glutathione peroxidase. In addition, the levels of tumor necrosis factor, interleukin-6 and interleukin-1β were reduced. Effects of lowering blood pressure and improving learning/memory ability in rats followed the order: lisinopril > black garlic nanoemulsion > black garlic extract.
2. Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy
Zaileen Ebrahim, Derek M Yellon, Gary F Baxter Pharmacol Res. 2007 Jan;55(1):42-8. doi: 10.1016/j.phrs.2006.10.004. Epub 2006 Oct 31.
Hypertensive left ventricular hypertrophy (LVH) co-exists frequently with ischaemic heart disease. While ischaemic preconditioning (IPC) is known to protect against ischaemia-reperfusion injury in LVH, it is not known if other cardioprotective manoeuvres are effective. Bradykinin, a key autacoid mediator in IPC, is protective in normal hearts but its ability to protect against ischaemia-reperfusion injury in LVH is unknown. Hypertensive LVH was induced in male rats by 4 weeks treatment with deoxycorticosterone acetate (DOCA) and salt drinking fluid. Hearts were Langendorff perfused, subjected to 35 min coronary artery occlusion and 120 min reperfusion, and infarct size (AN/RZ %) was determined by tetrazolium staining. The effects of IPC with 2 x 5 min cycles of global ischaemia or 10 min pretreatment with bradykinin were assessed. DOCA-salt rats were markedly hypertensive and left ventricle/body weight ratio was 26% greater than in normotensive controls. Baseline coronary flow and risk zone/LV ratio were similar in normotensive hearts and DOCA-salt hearts, and infarct size was similar (AN/RZ 50.6+/-3.2% and 47.0+/-3.1%, respectively). IPC was equally protective in normotensive and DOCA-salt hearts (AN/RZ 18.6+/-3.3% and 18.4+/-2.3%, respectively, P < 0.01 versus corresponding control). Bradykinin 0.1, 0.2 or 0.5 microM pretreatment produced concentration-dependent infarct limitation in normotensive hearts (bradykinin 0.5 microM AN/RZ, 9.5+/-3.6%, P < 0.01 versus normotensive control), but the effect in DOCA-salt hearts was attenuated (bradykinin 0.5 microM AN/RZ, 23.4+/-3.8%). Further, the pre-ischaemic coronary vasodilator response to bradykinin was abrogated in DOCA-salt hypertensive hearts. We conclude that the cardioprotective action of bradykinin is markedly attenuated in moderate LVH and coronary vasodilator effect is lost. The reasons for reduced sensitivity to bradykinin in the hypertensive heart are unknown but these findings may have implications for the application of preconditioning-mimetic interventions in LVH.
3. Omapatrilat increases renal endothelin in deoxycorticosterone acetate-salt hypertensive rats
Ahmed A Elmarakby, Peter Morsing, Jennifer S Pollock, David M Pollock Vascul Pharmacol. 2003 Dec;40(5):253-9. doi: 10.1016/j.vph.2004.01.002.
Vasopeptidase inhibitors are a new class of antihypertensive drugs that are single molecules having dual inhibitory action on angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The best known drug in this class is omapatrilat, which has been proposed to be more efficacious than ACE inhibitors because of its ability to inhibit NEP and prevent the breakdown of atrial peptides and bradykinin. However, survival of endothelin (ET) may also be enhanced and therefore, NEP inhibitors may have limited efficacy under conditions of low renin and high ET production. The purpose of the current study was to contrast the effects of the ACE inhibitor, enalapril, with omapatrilat in a model of established hypertension where ACE inhibitors are ineffective, the deoxycorticosterone acetate (DOCA)-salt-treated rat. Two weeks after starting DOCA-salt treatment, rats were given either enalapril (10 mg/kg/day) or omapatrilat (30 mg/kg/day) for 5 days. Mean arterial pressure (MAP) measured by radiotelemetry in untreated DOCA-salt rats increased from 102 +/- 2 to 181 +/- 12 mm Hg (P<.05) as a result of DOCA-salt treatment for 3 weeks. MAP was unaffected by either enalapril (189 +/- 3 mm Hg) or omapatrilat (184 +/- 8 mm Hg). DOCA-salt treatment significantly increased urinary ET excretion compared to baseline (1.6 +/- 0.2 vs. 0.5 +/- 0.1 pmol/day). Administration of omapatrilat significantly increased urinary ET excretion in DOCA-salt rats (2.9 +/- 0.4 pmol/day) compared to enalapril-treated (1.6 +/- 0.2 pmol/day) or untreated (1.5 +/- 0.1 pmol/day) rats. These results indicate that combined ACE/NEP inhibition does not lower blood pressure in a model of established hypertension with high ET activity. These results also support the hypothesis that combined ACE/NEP inhibition can increase renal ET production.
