TABLE 2.
Description and main results of the studies (in vivo, ex vivo) characterizing the effect of caffeic acid and its derivatives on cardiovascular physiological variables (CA–caffeic acid; CAPE–caffeic acid phenethyl ester; CAPA–caffeic acid phenethyl amide; w.o.–weeks old; CAO–coronary artery occlusion; MCAO–middle cerebral artery occlusion).
| Authors | Species/strain (sample size, age, weight), experimental procedure and anesthetic scheme | Drug | Drug dose and administration route | Effect on cardiovascular physiological variables |
| Leeya et al. (2010) | Healthy adult female Wistar rats (N = 6, 210–250 g) under pentobarbital anesthesia | CA | 1–10 mg/kg administered intravenously | Mean blood pressure and heart rate decreased only at a 10 mg/kg dose |
| Zhou et al. (2006) | Adult male Wistar rats (N = 6, 210–250 g) subjected to middle cerebral artery occlusion (MCAO) under chloral hydrate anesthesia | CA | 10 and 50 mg/kg administered intraperitoneally 30 min before MCAO, 0,1 and 2 h after reperfusion on the first day, then twice daily from days 2 to 5 | No difference in blood pressure and cerebral blood flow among sham, ischemic and ischemic + CA groups |
| Yokozawa et al. (1995) | Male Wistar rats (N = 6; 200–210 g) with adenine-induced renal failure and consequent hypertension (no anesthesia) | CA | 10 mg/kg administered orally in drinking water for 24 days | No difference in systolic and mean blood pressure |
| Agunloye et al. (2019) | Cyclosporine-induced hypertensive rats (N = 6, undisclosed strain, gender, age and weight; no anesthesia) | CA | 10 mg/kg/day and 15 mg/kg/day orally administrated for 7 days | Significant decrease in systolic blood pressure and heart rate |
| Iraz et al. (2005a) | Healthy male Sprague-Dawley rats (N = 6; 12 w.o.; 250–300 g) under urethane anesthesia | CAPE | 1, 5, 10, and 20 mg/kg administered intravenously | Dose-dependent decrease in mean blood pressure and heart rate; 1 mg/kg lowered the mean blood pressure up to 20 s and 5 and 10 mg/kg up to 2 min; 10 mg/kg decreased heart rate up to 10 min; 20 mg/kg caused death after a few seconds |
| Iraz et al. (2005b) | Healthy (N = 8) and bivagotomized (N = 8) male Sprague Dawley rats (12 w.o.; 250–300 g) under urethane anesthesia | CAPE | 5 mg/kg administered intravenously | The mean blood pressure was lowered up to 1 min |
| Hassan et al. (2014) | Healthy, insulin-resistant and insulin-resistant male Wistar rats (N = 8; 85–155 g; undisclosed age) without anesthesia | CAPE | 30 mg/kg/day administered orally by gavage for 6 weeks | In healthy animals, systolic, diastolic and pulse blood pressure did not change |
| In insulin-resistant and insulin-deficient animals, CAPE alleviated the increase in systolic, diastolic and pulse blood pressure | ||||
| Gun et al. (2016) | High fructose consumer Sprague Dawley rats (8 w.o.; undisclosed gender and weight) without anesthesia | CAPE | 50 μmol/kg/day administered intraperitoneally for 2 weeks | CAPE significantly ameliorated the increase in blood pressure that accompanied vascular damage |
| Eşrefoglu et al. (2005) | Male Wistar rats (N = 8; 250–350 g; undisclosed age) subjected to CAO under urethane anesthesia | CAPE | 50 μmol/kg administered intravenously 10 min before and during occlusion | CAPE prevented the drop in blood pressure induced by I/R injury and accelerated recovery to pre-injury values |
| Cagli et al. (2005) | Male Wistar rats (250–350 g, undisclosed age and sample size) subjected to CAO under thiopental anesthesia | CAPE | 10 μmol/kg administered intravenously 10 min before occlusion | No differences in heart rate between the control and CAPE-treated groups |
| Ozer et al. (2004) | Male Wistar rats (N = 7; 250–350 g) subjected to CAO under urethane anesthesia | CAPE | 1.25 μM/kg/min administered intravenously 10 min before and during occlusion by infusion | No changes in blood pressure and heart rate between the control and CAPE-treated animals |
| Parlakpinar et al. (2005) | Male Wistar rats (N = 8; 10–12 w.o.; 200–250 g) subjected to CAO under urethane anesthesia | CAPE | 50 μmol/kg administered intravenously before and during occlusion | No difference in heart rate or blood pressure in the control, ischemic or CAPE-treated groups. CAPE exerted no effect during ischemia or reperfusion |
| Altuǧ et al. (2008) | New Zealand white male rabbits (N = 6; 2.5–3 kg) subjected to MCAO under ketamine, xylazine and atropine anesthesia | CAPE | 10 μmol/kg/day intraperitoneally after MCAO for 7 days | No differences in blood pressure in CAPE-treated and control groups |
| Khan et al. (2007) | Male Sprague–Dawley rats (240–260 g; undisclosed age and sample size) subjected to MCAO under xylazine-ketamine anesthesia | CAPE | 1,2,5, and 10 mg/kg administered intravenously during MCAO or after reperfusion | No difference in blood pressure and heart rate between the control and animals treated with CAPE during cerebral I/R injury |
| Cerebral blood flow increased significantly at a dose of 2 mg/kg in comparison to controls | ||||
| Tsai et al. (2006) | Male Long–Evans rats (270–350 g) subjected to MCAO under halothane anesthesia | CAPE | 0.01, 0.1, 1, or 10 μg/kg administered intravenously 15 min before MCAO | No significant changes in heart rate or blood pressure between groups |
| Fadillioglu et al. (2004) | Male Sprague-Dawley rats (60 days old) receiving doxorubicin under urethane anesthesia | CAPE | 10 μmol/kg/day administered intraperitoneally for 12 days | CAPE attenuated the doxorubicin-induced increase in heart rate and blood pressure |
| Mollaoglu et al. (2006) | Adult males Wistar Albino rats (N = 12; 8 w.o., 280 g) receiving cadmium chloride i.p., for 15 days (undisclosed use of anesthesia) | CAPE | 10 μmol/kg/day administered intraperitoneally for 15 days | No significant changes in heart rate or blood pressure |
| Castellano et al. (2016) | Male Sprague Dawley rats (275–325 g; undisclosed age and sample size) | CAPE | 40 μM | In heart preparations CAPE restored L-NAME-induced compromise in left ventricle diastolic and end-systolic pressures after I/R injury |
| Chang et al. (2013) | Adult male Hartley guinea-pigs (300–350 g, N = 9–10; undisclosed age) | CAPE | 1, 3, and 10 μM for cardiac electrical conduction studies | Negative chronotropic effect and frequency-dependent depression of AV nodal conduction. |
| Reduction in the occurrence of reperfusion-induced ventricular fibrillation | ||||
| 3, 10, 30, 100 μM for cardiac contraction studies | Decrease in left ventricular pressure | |||
| Ho et al. (2013) | Healthy (N = 5) and diabetic (N = 9) male Wistar rats (8 w.o.; 250–300 g), under sodium pentobarbital anesthesia | CAPA | 1, 3, and 10 μM intravenously in heart preparations | No change in heart rate |
| CAPA | 1, 5, and 10 mg/kg administered orally by gavage | No changes in blood pressure (data not shown in paper) |