Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension

Abstract

Parasympathetic nerves from the pterygopalatine ganglia provide nitroxidergic innervation to forebrain cerebral blood vessels. Disruption of that innervation attenuates cerebral vasodilatation seen during acute hypertension as does systemic administration of a non-selective nitric oxide synthase (NOS) inhibitor. Although such studies suggest that nitric oxide (NO) released from parasympathetic nerves participates in vasodilatation of cerebral vessels during hypertension that hypothesis has not been tested with selective local inhibition of neuronal NOS (nNOS). We tested that hypothesis through these studies performed in anesthetized rats instrumented for continuous measurement of blood pressure, heart rate and pial arterial diameter through a cranial window. We sought to determine if the nNOS inhibitor propyl-L-arginine delivered directly to the outer surface of a pial artery would 1) attenuate changes in pial arterial diameter during acute hypertension and 2) block nNOS mediated dilator effects of N-methyl-D-Aspartate (NMDA) delivered into the window but 3) not block vasodilatation elicited by acetylcholine (ACh) and mediated by endothelial NOS dilator. Without the nNOS inhibitor arterial diameter abruptly increased 70 ± 15% when mean arterial pressure (MAP) reached 183 ± 3 mmHg while with nNOS inhibition diameter increased only 13 ± 10% (p<0.05) even when MAP reached 191 ± 4 (p>0.05). The nNOS inhibitor significantly attenuated vasodilatation induced by NMDA but not ACh delivered into the window. Thus, local nNOS inhibition attenuates breakthrough from autoregulation during hypertension as does complete interruption of the parasympathetic innervation of cerebral vessels. These findings further support the hypothesis that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension. Section: Regulatory Systems

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…␤-Adrenoceptors and nNOS-derived NO seem to interact in contributing to hypoglycemia-induced cerebral vasodilatation, and the vasodilating signal may be transmitted via a neuronal pathway. In anesthetized rats, without the nNOS inhibitor propyl-L-arginine, the pial arterial diameter abruptly increased when mean arterial pressure rose, whereas with nNOS inhibition the diameter increased to a much lesser extent even when arterial pressure was similarly raised; the nNOS inhibitor attenuated pial arterial dilatation induced by NMDA but not that induced by ACh delivered into a cranial window (Talman and Nitschke Dragon, 2007). NO released from parasympathetic fibers seems to contribute to cerebral vasodilatation during acute hypertension.…”

“…Erythrocyte velocity in rat cerebral capillaries increased, as arterial hematocrit was reduced; pretreatment with 7-NI abolished the increase in velocity, leading to the conclusion that NO from a neural source may contribute to the increase in capillary erythrocyte flow during hemodilution . There was evidence suggesting that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension in anesthetized rats (Talman and Nitschke Dragon., 2007). On the other hand, Stefanovic et al (2007) found that 7-NI had no effect on cerebral blood flow in anesthetized rats.…”

Control of systemic and pulmonary blood pressure by nitric oxide formed through neuronal nitric oxide synthase

“…The role of nNOS-derived nitric oxide in cerebral vasodilatation in rats has been determined [47][48][49]. Pial artery diameter in rats increased when mean arterial pressure was raised, and this effect was inhibited by the nNOS inhibitor propyl-L-arginine; vasodilatation induced by NMDA, but not by ACh, was attenuated by the nNOS inhibitor [50]. The authors suggested that nitric oxide released from parasympathetic nitrergic nerves participates in cerebral vasodilatation during acute hypertension.…”

Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation

“…Extrinsic innervation of arterial vessels seems not to be involved, as demonstrated by the preservation of autoregulation in sympathetically and parasympathetically denervated animals [24]. On the other hand, intrinsic innervation may be involved, as well as metabolic modulation through the release of nitric oxide, adenosine and other vasoactive substances [25,26].…”