Mesenteric arterial function in vitro in three models of experimental hypertension.

OBJECTIVE

To investigate arterial function in three models of experimental hypertension.

METHODS

Twenty-five-week-old spontaneously hypertensive rats (SHRs), deoxycorticosterone-sodium chloride-treated Wistar-Kyoto rats (DOCs), and obese Zucker rats (OZRs) were used. Untreated Wistar-Kyoto rats (WKYs) and lean Zucker rats (LZRs) served as normotensive control rats. The function of mesenteric arterial rings was investigated in organ baths.

RESULTS

In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and nitroprusside were reduced in SHRs, DOCs, and OZRs. NG-nitro-L-arginine methyl ester attenuated the dilations to ACh effectively in all study groups, the inhibitory effect being more potent in SHRs and DOCs and similar in OZRs when compared with corresponding controls. Unlike in norepinephrine-precontracted rings, the relaxations to ACh during precontraction with 60 mmol/l potassium chloride (prevention of endothelium-dependent hyperpolarization) were not impaired in the hypertensive animals. Nifedipine inhibited the contractile responses induced by cumulative addition of Ca2+ during stimulation with norepinephrine more effectively in SHRs and DOCs than in WKYs, whereas no such difference was seen between OZRs and LZRs.

CONCLUSIONS

Experimental models of genetic, mineralocorticoid-sodium chloride-induced, and obesity-related hypertension were associated with attenuated arterial dilation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-nitric oxide pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle from SHRs and DOCs, whereas such an abnormality was not observed in obesity-related hypertension.