Characterization and Antihypertensive Effect of the Complex of (-)-β- pinene in β-cyclodextrin.
This work aimed to characterize and evaluate the antihypertensive effect of the (-)-β-pinene/β-cyclodextrin (βP/β-CD) complex. The complex was prepared through physical mixture and slurry complexation methods and was analyzed through differential scanning calorimetry, thermogravimetry/derivative thermogravimetry, fourier transform infrared spectroscopy, diffraction X-ray, docking and scanning electron microscopy. Normotensive or L-NAME-induced hypertensive rats were used in pharmacological experiments. Mean arterial pressure (MAP) was determined with direct blood pressure measurements from the abdominal aorta. The drugs were orally administrated and their effects were recorded during 48 hours. Vascular effects of βP were evaluated in isolated ring of mesenteric artery. The physicochemical characterization showed βP/β-CD complex formation. In hypertensive rats (MAP = 156±16 mmHg), the complex, but not βP alone, promoted hypotension at 36 and 48 hours after administration (MAP = 124±3 and 110±5 mmHg, respectively). In arterial rings, βP vasorelaxed rings precontracted with phenylephrine (Emax = 105±6%), which was not changed after the removal of the vascular endothelium (Emax = 108±4%), after the pre-contraction with KCl 80 mM (Emax = 107±8%) or S(-)-BayK8644 (Emax = 107±5%), or after incubation with TEA (Emax = 113±4%). Finally, βP inhibited CaCl2- and sodium-orthovanadate-induced contractions. In conclusion, the slurry complexation method was the best among them. Pharmacological results demonstrated that the complex promoted antihypertensive effect. Furthermore, βP induced endothelium- independent vasorelaxation possibly caused by the inhibition of the Ca2+ influx through L-type Ca2+ channel associated to a decrease in calcium sensitivity.
Italo J A
IJ
Moreira
Paula P
PP
Menezes
Mairim R
MR
Serafini
Adriano A S
AA
Araújo
Lucindo J
LJ
Quintans-Júnior
Leonardo R
LR
Bonjardim
Valter J S
VJ
Filho
Daniel
D
B P Júnior
Sandra L
SL
Santos
Waldecy L
WL
Júnior
Luciana
L
Scotti
Marcus T
MT
Scotti
Department of Physiology, Universidade Federal de Sergipe, São Cristovao - SE, 49100-000, Brazil. marciorvsantos@hotmail.com.
Márcio R V
MR
Santos
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects; D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010656:Phenylephrine / Q000494:pharmacology; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds; D039821:Monoterpenes; D014662:Vasoconstrictor Agents; D047392:beta-Cyclodextrins; D010656:Phenylephrine; C010789:beta-pinene; C031215:betadex; D002118:Calcium