The effect of clonidine on vascular reactivity to angiotensin, noradrenaline, and vasopressin in conscious rats

Abstract

The critical opening pressure (COP) of small vessels in the tails of conscious rats was measured by the spectroscopic technique as an index of arteriolar smooth muscle contraction force. In 11 rats acute intramuscular injection of clonidine (15 μg/kg) decreased systolic blood pressure (SBP) and COP by 13.7 ± 1.7 (SEM) and 7.6 ± 1.1 mmHg, respectively, in intact rats but increased SBP by 30.4 ± 2.6 and COP by 25.9 ± 3.5 mmHg in six ganglion-blocked rats. Reactivity of arteriolar muscle was measured as the increase in COP of the vessels in response to intravenous infusion at three or four dose levels of angiotensin II (2–12 ng kg⁻¹ min⁻¹), noradrenaline (30–120 ng kg⁻¹ min⁻¹), or lysine-8-vasopressin (0.085–0.34 mU kg⁻¹ min⁻¹). The dose–response relationship was considered to be essentially linear and increases in COP in clonidine-treated and control rats were compared directly. Acute administration of clonidine (1, 3, or 10 μg/kg, im) decreased vascular reactivity to each of these agents in both the intact and ganglion-blocked rat. For example, in ganglion-blocked rats total increases in COP were as follows: (1) during infusion of angiotensin (8 ng kg⁻¹ min⁻¹), 22.3 ± 1.3 (SEM) mmHg in clonidine-treated rats and 40.3 ± 3.7 in controls (p < 0.01); (2) during infusion of noradrenaline (120 ng kg⁻¹ min⁻¹), 8.4 ± 1.7 mmHg in clonidine-treated rats and 30.0 ± 2.6 in controls (p< 0.001); and (3) during infusion of vasopressin (0.34 mU kg⁻¹ min⁻¹), 24.8 ± 0.3 mmHg in clonidine-treated rats and 47.8 ± 0.9 in controls (p < 0.001). Chronic treatment of rats with clonidine (20 μg kg⁻¹ day⁻¹) for 7 or more days had a similar effect on vascular reactivity. This apparently nonspecific reduction of vascular reactivity could play an important part in the antihypertensive effect of clonidine hydrochloride.