Mechanisms involved in the hypotensive effect of a kappa-opioid receptor agonist in hypertensive rats.
BACKGROUND
It remains unclear whether the activation of kappa-opioid receptors has strong hypotensive effects under hypertensive condition, and the underlying mechanisms have not yet been investigated. Therefore, the present study is designed to use spontaneously hypertensive rats (SHR) to investigate the effects of a kappa-opioid receptor agonist on the regulation of urinary formation in hypertensive conditions and to identify its underlying mechanism.


METHODS
The hemodynamics, urine flow rate, vasodilatation of isolated renal artery, and plasma hormones were determined by physiological in vivo experimental technique, isolated artery perfusion technique and radioimmunoassay.


RESULTS
Intravenous administration of U50, 448H significantly decreased mean arterial blood pressure in both Wistar-Kyoto (WKY) rats and SHR. However, the blood pressure vasodepressor effect of U50, 448H was much more profound in SHR than in WKY rats. Administration of U50, 448H in SHR not only caused significantly greater effects in increasing urine volume and decreasing plasma anti-diuretic hormone than in WKY rats, but also caused significant reduction in plasma angiotensin. Moreover, vasodilatory effect of U50, 488H was significantly exhibited in the renal artery segments isolated from SHR. All effects described above were abolished by nor-binaltorphimine.


CONCLUSIONS
These data indicate that the depressor effect of U50, 488H in SHR is significantly stronger than that in WKY rats, and the effect is mediated or modulated by a kappa-opioid receptor sensitive mechanism. The sensitized hypotensive effect of U50, 488H in SHR may be attributed, in part, to its vasodilatory effect, enhanced beneficial effect on plasma humoral factors, and stronger diuretic effect in these hypertensive animals.
Guo
Hai-Tao
HT
Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Zhang
Rong-Huai
RH
Huang
Lu-Yu
LY
Li
Juan
J
Liu
Ya-Li
YL
Bi
Hui
H
Zhang
Quan Yu
QY
Wang
Yue-Min
YM
Sun
Xin
X
Ma
Xin-Liang
XL
Cheng
Liang
L
Liu
Jing-Cheng
JC
Yu
Shi-Qiang
SQ
Yi
Ding-Hua
DH
Pei
Jian-Ming
JM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage* / Q000494:pharmacology*; D000809:Angiotensins / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D012077:Renal Artery / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014667:Vasopressins / Q000097:blood
D000809:Angiotensins; D000959:Antihypertensive Agents; D017473:Receptors, Opioid, kappa; D014667:Vasopressins; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer