Enhanced vascular reactivity in the sympathectomized rat: studies in vivo and in small isolated resistance arteries

OBJECTIVE: In the conscious rat, sympathectomy (6-hydroxydopamine pretreatment, 100 mg/kg intraperitoneally, twice in the previous 5-6 days) induces, among various homeostatic modifications, the frequent occurrence of sudden and wide oscillations of blood pressure. Since one of the mechanisms underlying this, as yet unexplained, phenomenon may be an enhanced vascular reactivity, we tested the hypothesis that sympathectomized rats exhibit such a hyper-reactivity. We examined the response to a variety of vasoactive agents both in vivo (chronically instrumented conscious animals) and in vitro (small isolated resistance arteries). DESIGN AND METHODS: Wistar-Kyoto sympathectomized rats (6-hydroxydopamine pretreatment, n = 19) and control rats (vehicle pretreatment, n = 23) were studied. In conscious animals, concentration-blood pressure response curves to intra-venous bolus injections of vasopressin, phenylephrine and angiotensin II were obtained. In isolated vessels, concentration-wall tension response curves were obtained for norepinephrine, phenylephrine, vasopressin, serotonin and potassium. Vasodilator responses to acetylcholine (with or without L-NAME), bradykinin and sodium nitroprusside were also evaluated after precontraction with norepinephrine (mesenteric arteries) or vasopressin (cerebral arteries). RESULTS: In sympathectomized rats in vivo the pressor responses to vasopressin, phenylephrine and angiotensin II were significantly larger than in control rats, the difference amounting to 46.5, 40.2 and 57.1%, respectively (all P < 0.05). In vitro, the vascular reactivity of isolated cerebral arteries was similar in sympathectomized and control rats. In contrast, the mesenteric arteries showed significantly increased contractions in sympathectomized compared to control rats in response to norepinephrine, phenylephrine and vasopressin but not to serotonin and potassium, whereas the vasodilator responses to acetylcholine and sodium nitroprusside (but not to bradykinin and acetylcholine+L-NAME) were reduced. CONCLUSIONS: In conclusion, we showed that sympathectomy produces complex alterations of vascular reactivity both in vivo and in isolated vessels, which shift the balance of the sensitivity of the vessel between vasoconstrictor and vasodilating agents towards an increased constriction. These results are unlikely to simply reflect denervation supersensitivity; their underlying receptor, post-receptor and/or contractile mechanisms are yet to be identified.