Table 4.
Effects of melatonin and blood pressure.
| Drug or pharmacological agent | Melatonin dose | Treatment duration | Targets | Effects | Model | Disease or condition | References |
|---|---|---|---|---|---|---|---|
| Melatonin | – | – | – | Ameliorated hypertension in pregnant mice | In vivo (mice) | Gestational hypertension | (342) |
| Melatonin | 6 mg/d | 8 weeks | – | Controlled blood pressure | Humans | Type 2 diabetes mellitus | (343) |
| Melatonin | 10 mg/kg/d | 11 days | Antioxidant capacity, plasma MDA, sFlt-1, Nrf2, PlGF, HO-1 | Markedly lowered blood pressure | In vivo (rats) | L-NAME-associated pre-eclampsia | (344) |
| Melatonin | 6 mg/d | 12 weeks | – | Improved blood pressure | Humans | Non-alcoholic fatty liver disease (NAFLD) | (345) |
| Melatonin | 30 mg/kg/d | 15 days | ROS | Effectively reduced baseline MAP | In vivo (rats) | Neurogenic hypertension | (346) |
| Melatonin | 24 mg/d | 4 weeks | – | No statistical effect on nighttime or daytime systolic or diastolic blood pressure | Humans | Essential hypertension | (347) |
| Melatonin | 10 mg/kg/day | 4 weeks | Renin-angiotensin-aldosterone system (RAAS) | Reduced systolic blood pressure | In vivo (rats) | L-NAME-induced hypertension | (307) |
| Melatonin | 10 mg/d | 12 weeks | NO, MDA, protein carbonyls (PCO), HDL-cholesterol, hs-CRP | Improved blood pressure | Humans | Type 2 diabetes & CAD | (348) |
| Melatonin | 5 mg/kg/d | 20 days | TNF-a, IL-6, VEGF, sFlt-1 | Decreased blood pressure | In vivo (rats) | Pre-eclampsia | (349) |
| Melatonin | 10 mg/kg/d | 6 weeks | NOS, NF-κB | Had no effect on SBP | In vivo (rats) | Lactacystin-induced hypertension | (350) |
| Melatonin | 5 mg/kg/d | 3 weeks | KCNQ & KCNH2 genes | Prevented increase in blood pressure | In vivo (rats) | Pinealectomy & L-NAME-induced hypertension | (351) |
| Melatonin | 10 μM | 6, 12, 18, 24 h | Endothelin, Ang II, NO, eNOS | Circadian antihypertensive effects | In vitro (HUVECs) | Hypertension | (320) |
| Melatonin | 10 mg/kg/d | 3 weeks | eNOS & nNOS protein expression | Decreased blood pressure | In vivo (rats) | Metabolic syndrome | (314) |
| Melatonin | 6 mg | – | Lowered systolic, diastolic & mean blood pressure | Humans | Laryngoscopy & endotracheal intubation | (352) | |
| Melatonin | 5 mg/kg | Cortisol, Ang I, Ang II, aldosterone, ANP, CRH, ACTH, endothelin | Reduced fetal hypertension | In vivo (sheep) | Fetal blood pressure | (317) | |
| Melatonin | 5 mg/kg/d | 6 weeks | MDA, uric acid, renal aquaporin-3 (AQP-3) | Decreased systolic blood pressure | In vivo (rats) | Metabolic syndrome | (353) |
| Melatonin | 1.5 mg/d | 2 weeks | – | Reduced SBP & DBP levels | Humans | Elderly | (354) |
| Melatonin | 3, 5 mg/d | 8 weeks | - | Regulated blood pressure in circadian rhythm, reduced nocturnal hypertension | Humans | Type 2 diabetes & hypertension | (355) |
| Melatonin | 0.01% melatonin in drinking water | Entire duration of pregnancy & lactation | Ephx2, Col1a2, Gucy1a3, Npr3, Aqp2, Hba-a2, Ptgs1 genes, NO, soluble epoxide hydrolase (SEH) | Blunted maternal high fructose (HF)-induced hypertension | In vivo (rats) | Maternal HF-induced hypertension | (326) |
| Melatonin | 0.01% melatonin in drinking water | Entire duration of pregnancy & lactation | Renal superoxide, NO, renin–angiotensin system, Mas protein, histone deacetylase (HDAC)-1, HDAC-2, HDAC-8 | Attenuated prenatal DEX induced hypertension | In vivo (rats) | Dexamethasone-induced hypertension | (322) |
| Melatonin | 10 mg/kg/d | 6 weeks | – | Partially prevented increased systolic blood pressure | In vivo (rats) | Continuous light-induced hypertension | (356) |
| Melatonin | 25 μg/mL in drinking water | 10 weeks | Hypophysial-testicular axis | Significantly blunted SBP | In vivo (rats) | Metabolic syndrome | (357) |
| Melatonin | 0.01% melatonin in drinking water | 6 weeks | Asymmetric dimethylarginine (ADMA), arginine, dimethylarginine dimethylaminohydrolase (DDAH), NO, 8-hydroxydeoxyguanosine | Lowered blood pressure | In vivo (rats) | Spontaneous hypertension + L-NAME | (312) |
| Piromelatine (melatonin agonist) | 5, 15, 50 mg/kg/d | 5 weeks | Plasma glucose, insulin, triglyceride, adiponectin, total cholesterol, HDL & LDL/VLDL cholesterol | Reduced blood pressure | In vivo (rats) | Spontaneous hypertension | (358) |
| Melatonin | 10 mg/kg/d | ||||||
| Melatonin | 10 mg/kg/d | 4 weeks | Oxidative stress | Prevented doxorubicin-induced increase in systolic blood pressure | In vivo (rats) | Doxorubicin-induced nephrotoxicity | (359) |
| Melatonin | 10 mg/kg/d | Beginning of pregnancy up to 3rd week postpartum | Renal GPx, glutathione s-transferase (GST), total glutathione, SOD, catalase, glutathione reductase | Lowered systolic blood pressure, delayed but not completely eliminated hypertention | In vivo (rats) | Spontaneous hypertension | (360) |
| After weaning until 16 weeks | |||||||
| Melatonin | 5 mg/d | 2 months | Glucose, serum lipids, C-reactive protein, fibrinogen, catalase, GPx, SOD, TBARS | Lowered blood pressure | Humans | Metabolic syndrome | (361) |
| Melatonin | 10 mg/kg | 5 weeks | Conjugated dienes, NOS, COX-1, COX-2 | Slight antihypertensive effect | In vivo (rats) | L-NAME-induced hypertension | (362) |
| Melatonin | 5 mg/d | 90 days | – | Decreased nocturnal blood pressure, increased daytime blood pressure | Humans | Coronary artery disease, circadian hypertension | (363) |
| Melatonin | 10 mg/kg/d | 5 weeks | NOS, eNOS, NF-κB, conjugated dienes, collagenous proteins, hydroxyproline | Reduced systolic blood pressure | In vivo (rats) | Spontaneously hypertensive rats | (364) |
| Melatonin | 1 mg/kg/d | 15 days | Angiotensin II, GABA(A) receptors | Prevented blood pressure increase, reduced blood pressure in developed hypertension | In vivo (rats) | Stress-induced hypertension | (365) |
| Melatonin | 0.1 μL of 0.1 or 1.0 mM | 14 days | Glutamate, GABA, taurine, MT1, MT2, and MT3 | Reduced blood pressure | In vivo (rats) | Stress-induced hypertension | (366) |
| Melatonin | 2 mg/d | 4 weeks | – | Reduced nocturnal systolic blood pressure | Humans | Nocturnal hypertension | (367) |
| Melatonin | 10 mg/kg | 5 days | – | Reduced blood pressure | In vivo (rats) | L-NAME-induced hypertension | (368) |
| Melatonin | 3 mg/d | 3 weeks | – | Reduced nocturnal blood pressure | Humans (women) | Essential hypertension | (369) |
| Melatonin | 10 mg/d | 7 days | – | Lowered blood pressure | Humans | Type 1 diabetes | (370) |
| Melatonin | 5 mg/d | 1 week | – | Reduced nocturnal diastolic blood pressure | Humans | Type 1 diabetes | (371) |
| Melatonin | 2.5 mg/d | 3 weeks | – | Reduced nocturnal blood pressure | Humans | Essential hypertension | (88) |
| Melatonin | 0.1 μL of 0.1 or 1.0 mM | 15 days | ML1, ML2 receptors | Reduced mean arterial pressure | In vivo (rats) | Stress-induced hypertension | (372) |
| Melatonin | 2.5, 5 mg/kg | – | Did not affect blood pressure | In vivo (rats) | – | (373) | |
| Melatonin | 1 mg | 2 days | – | Reduced blood pressure | Humans (men) | – | (374) |
| Melatonin | 10, 50 ng/kg | – | Reduced blood pressure | In vivo (Atlantic cod) | – | (375) | |
| Melatonin | 5 mg/d | 4 weeks | – | Reduced blood pressure | Humans | Normotensive | (376) |