Adrenergic neurotransmission in vascular smooth muscle from spontaneously hypertensive rats

The goal of this study was to compare adrenergic neurotransmission in isolated vascular smooth muscle from spontaneously hypertensive (SHR) and normotensive rats. Tail arteries, excised from adult SHR and normotensive rats, were cut helically into strips that were mounted in organ chambers between two platinum wire electrodes; isometric contractions were recorded. Vascular responsiveness was determined before and after acute denervation with 6-hydroxydopamine or before and after treatment with phentolamine. Release or displacement of endogenous norepinephrine was obtained with electrical stimulation, tyramine, and potassium. The sensitivity to exogenous norepinephrine of innervated vessels was similar for SHR and normotensive rats. Denervation produced a significant shift to the left in the concentration-response curve to norepinephrine only in SHR vessels. Contractile responses to electrical stimulation, tyramine, and potassium were similar in both groups before denervation. Contractile responses to potassium-free solution were greater in SHR than in normotensive vessels. Following denervation, the SHR and normotensive vessels responded similarly to these latter interventions. Blockade of alpha-adrenoceptors with phentolamine reduced contractile responses to all agents in innervated and denervated vessels. Cocaine caused a slowing of the relaxation following contraction induced by electrical stimulation in both SHR and normotensive vessels. The relaxation of SHR vessels was less affected by cocaine than in normotensive vessels. The tissue content of norepinephrine was similar in SHR and normotensive arterial strips. In arterial strips from SHR the uptake of 3H-norepinephrine was significantly larger than in those from normotensive rats. The results suggest that the reactivity of innervated blood vessels to norepinephrine is similar in SHR and normotensive rats. Important differences in sensitivity to norepinephrine in hypertensive vessels are unmasked when the relationship between the vascular smooth muscle cell and the adrenergic nerve terminal is altered. Apparently, the adrenergic nerve terminals in hypertensive blood vessel can modulate the junctional concentration of norepinephrine so that the contractile response to this agent is similar to that in normotensive blood vessels.link_to_subscribed_fulltex