Central hypotensive action of clonidine requires nitric oxide.
نویسندگان
چکیده
Background- Clonidine has an antihypertensive effect by its action in the brain and, because we observed that the tonic production of nitric oxide (NO) in the brain is required to maintain blood pressure at its low, normotensive level, the current study was designed to determine whether the hypotensive action of clonidine resulted from its stimulation of excess NO in the brain. Methods and Results- Porphyritic microsensors were used to quantify NO concentration in the nucleus tractus solitarius (NTS) in vitro in brain slices and in vivo in the anesthetized rat. In both preparations, the basal production of NO in the NTS was 15+/-3 nmol/L. In vitro stimulation of the NTS with clonidine (50 nmol/L) resulted in an increase in the NO concentration to 84+/-7 nmol/L. In vivo, the intracerebroventricular (ICV) infusion of clonidine (0.03 microgram) caused an increase in NO concentration in the NTS to 128+/-17 nmol/L. This ICV injection of clonidine caused a fall in mean arterial pressure of -22+/-1 mm Hg and a decrease of heart rate of -18+/-2%. The blockade of NO production with N(G)-nitro-L-arginine-methyl ester (2 micromol; delivered ICV, 30 minutes before the clonidine) reduced responses to clonidine for both mean arterial pressure and heart rate (-3+/-1 mm Hg and -2+/-1% change, respectively). Conclusion- The stimulation of the release of NO in the brain by clonidine contributes to its central antihypertensive action.
منابع مشابه
Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines.
NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of gamma-aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmen...
متن کاملBrainstem phosphorylated extracellular signal-regulated kinase 1/2-nitric-oxide synthase signaling mediates the adenosine A2A-dependent hypotensive action of clonidine in conscious aortic barodenervated rats.
The cellular mechanisms that underlie the enhancement of clonidine-evoked hypotension in aortic barodenervated (ABD) rats and its dependence on central adenosine A(2A) receptor (A(2A)R) are not known. We tested the hypothesis that A(2A)R-mediated phosphorylation of extracellular signal-regulated kinase (pERK)1/2 in the rostral ventrolateral medulla (RVLM) and its downstream activation of nitric...
متن کاملBrainstem adenosine A1 receptor signaling masks phosphorylated extracellular signal-regulated kinase 1/2-dependent hypotensive action of clonidine in conscious normotensive rats.
Central adenosine A(1) and A(2A) receptors mediate pressor and depressor responses, respectively. The adenosine subtype A(2A) receptor (A(2A)R)-evoked enhancement of phosphorylated extracellular signal-regulated kinase (pERK) 1/2 production in the rostral ventrolateral medulla (RVLM), a major neuroanatomical target for clonidine, contributes to clonidine-evoked hypotension, which is evident in ...
متن کاملThe interaction between prazosin and clonidine.
1. The interaction between prazosin and clonidine was studied in anaesthetized rats, pithed rats and in anaesthetized cats. 2. Prazosin diminished the clonidine-induced hypotensive effect in anaesthetized rats, probably via an antagonism at the level of central alpha-adrenoreceptors. 3. In pithed rats, stimulation of the Nervi accelerantes caused tachycardia, which was diminished considerably b...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 104 16 شماره
صفحات -
تاریخ انتشار 2001