Copyright © 2005, European Society of Cardiology
Increased counteracting effect of eNOS and nNOS on an 
1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1103, Blindern, 0317 Oslo, Norway
* Tel.: +47 22851090, fax: +47 22851502. Email address: torill.berg{at}basalmed.uio.no
Objective: The hypertension in spontaneous hypertensive rats (SHR) may result from a hyperactive sympathetic nervous system or from insufficient bioactive nitric oxide (NO) due to increased oxidative stress. The present investigation aimed to elucidate the balance between these two systems by studying the ability of NO to oppose an adrenergic rise in total peripheral vascular resistance (TPVR).
Methods: In anesthetized, open-chest SHR and normotensive controls (WKY) on a respirator, blood pressure was recorded in the femoral artery and cardiac output measured by ascending aorta flow. Tyramine infusion (15 min, intravenously) was used to stimulate neuronal noradrenaline release.
Results: Tyramine induced an immediate but transient increase in TPVR, which was 4.5 times greater in SHR. After the non-selective NO synthase (NOS) inhibitor (L-NAME: N
-nitro-L-arginine methyl ester), 
TPVRimm was 8.6 and 5.3 times increased in SHR and WKY, respectively, and TPVR remained elevated throughout the infusion period. Addition of 
1-adrenoceptor antagonist (prazosin+L-NAME) abolished the TPVR response to tyramine. Neuronal NOS inhibitor (7-introindazole) increased TPVRimm only in SHR (2.1 times), and TPVR remained elevated. Inducible NOS inhibitor (1400W), free radical scavenger (tempol), NAD(P)H oxidase inhibitor (apocynin), angiotensin AT1 receptor antagonist (losartan), and ganglion blocker (hexamethonium) had no effect on the tyramine TPVR response in either strain. TPVR to hexamethonium, prazosin, and L-NAME were greater in SHR than WKY, and hexamethonium reduced TPVR to L-NAME in SHR only.
Conclusions: The 1-adrenoceptor TPVR response to endogenous noradrenaline release was increased in SHR. This was not due to reduced bioavailable NO; on the contrary, NO counteraction was greatly increased, derived from endothelial NOS, with an additional role of neuronal NOS not seen in WKY. An influence of oxidative stress on these responses was not detected in either strain. In addition, a central eNOS sympathoinhibitory component appeared to influence baseline TPVR in SHR.
KEYWORDS Autonomic nervous system; Hypertension; Oxygen radicals; Nitric oxide; Vasoconstriction/dilatation