# Nitrergic neurotransmission within the lateral hypothalamus modulates cardiovascular responses to stress in rats

## TL;DR

This study shows that nitric oxide signaling in the lateral hypothalamus of rats helps control heart rate and blood pressure during stress.

## Contribution

The study identifies a specific role of neuronal nitric oxide synthase in modulating cardiovascular responses to stress in the lateral hypothalamus.

## Key findings

- Inhibiting nNOS in the lateral hypothalamus enhanced heart rate responses to stress.
- Nitric oxide signaling in the lateral hypothalamus modulates cardiovascular adjustments during acute stress.
- The effect of nitrergic signaling appears to involve mechanisms independent of inducible NOS.

## Abstract

The lateral hypothalamus (LH) is a key brain region involved in integrating cardiovascular and autonomic components of the stress response, yet the local neurochemical mechanisms governing these functions remain poorly understood. This study examined the contribution of nitrergic neurotransmission within the LH to cardiovascular adjustments induced by acute restraint stress in rats. To this end, animals received bilateral microinjections into the LH of either the nonselective nitric oxide synthase (NOS) inhibitor L-NAME, the selective neuronal NOS (nNOS) inhibitor Nω-propyl-L-arginine hydrochloride (NPLA), the selective inducible NOS (iNOS) inhibitor 1400W, or the nitric oxide (NO) donor MAHMA NONOate (NOC-9) prior to the restraint session. Intra-LH administration of L-NAME significantly attenuated both the pressor and tachycardic responses elicited by restraint. In contrast, the selective nNOS inhibitor NPLA selectively enhanced the tachycardic response without altering the pressor effect or sympathetically-mediated cutaneous vasoconstriction. Consistent with the effect observed in NPLA-treated animals, facilitation of local nitrergic neurotransmission through intra-LH injection of the NO donor selectively reduced the heart rate response to restraint. The selective iNOS inhibitor 1400W did not affect any of the cardiovascular parameters measured. Taken together, these findings indicate that nitrergic signaling within the LH plays a critical role in modulating cardiovascular adjustments to acute stress. This regulation appears to involve a complex process involving nNOS and an additional nitrergic mechanism that acts independently of iNOS.

The online version contains supplementary material available at 10.1007/s00424-026-03161-4.