Endogenous nitric oxide as a physiological regulator of vascular tone in cat skeletal muscle during haemorrhage

Abstract

The problem whether endogenous nitric oxide (NO) may serve as a true physiological regulator of vascular tone in vivo was approached by testing its role during graded acute haemorrhage with the aid of the nitric oxide synthase (NOS) inhibitor L-NAME. The study was performed on the vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of vascular resistance in the whole vascular bed (RT) and in its consecutive sections, the proximal arterial resistance ('feeder') vessels (> 25 microns; Ra,prox), the small arterioles (< 25 microns) and the veins. NO blockade by close-arterial L-NAME infusion in the control situation increased RT from 16.3 to 33.0 PRU (+102%), because of a selective increase in Ra,prox by 16.7 PRU. A 35% blood loss per se raised RT from 13.6 to 21.7 PRU. Superimposed NO blockade in this state caused a much stronger vasoconstriction than in the control situation, increasing RT to 60.9 PRU (+181%) and Ra,prox by 40.5 PRU, which indicated an approximately 2.4-fold increase (P < 0.001) in the NO dilator influence in the Ra,prox section above control. The effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased production of endothelium-derived nitric oxide (EDNO), The constrictor response to L-NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regulator of vascular tone in the arterial 'feeder' vessels during haemorrhage, serving to counterbalance to a significant extent the concomitant adrenergic constriction, and thereby preventing critical reduction of blood flow and untoward heterogeneous flow distribution within the tissue.

Cardiovascular regulation by endogenous nitric oxide is essential for survival after acute haemorrhage

“…This concept is in agreement with our previous studies on the muscle circulation (Mellander & Ekelund 1995, Ekelund & Mellander 1996 which indicated that endothelium-derived nitric oxide (EDNO) is released in increased amounts during acute haemorrhage and then functions as an inhibitory regulator of vascular tone in the large-bore arterial resistance vessels, serving to counterbalance to a significant extent the concomitant reflex adrenergic constriction; thereby a critical reduction of blood flow and untoward heterogeneous flow distribution in the \ tissue are prevented. Loss of this vasodilator response 'tQ EDNO, most likely formed by a constitutive NOS .…”

Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

“…The administration of 1 mg?kg 21 body weight L-NAME in people with tetraplegia increased systemic blood pressure and lower leg vascular resistance to control group levels. Baroreceptor-dependent vasoregulation is an important mechanism for mitigating the potentially deleterious consequences of hypertensive episodes to the arterial endothelium (27)(28)(29). In the control group, buffering of the blood pressure response to NOS inhibition via the arterial baroreceptors and synergistic humoral pathways was present to modulate changes to vascular tone and, thus, vascular resistance (30,31); the observed arterial vasoconstrictor responses to NOS inhibition were the result of the sum of intact vasoregulatory pathways responding to the pressor effect of NOS inhibition.…”

“…In neurologically intact humans, rapid activation of endothelial-derived NOS and production of NO in response to abrupt and dynamic fluctuations of blood flow are essential to enable adequate perfusion of metabolically active organs/tissue during exercise or stressful situations (27,28), as well as for hyperemic dilatation (43) and the protection against pressuremediated injury to vital organs and tissues (29). The release of NO facilitates vasodilatation (43) and buffers the elevated arterial vascular resistance through a reduction of sympathetic nerve activity to the vascular smooth muscle (29).…”

α 2–Adrenoceptor activation may trigger the increased production of endothelium–derived nitric oxide in skeletal muscle during acute haemorrhage

“…Our previous studies have indicated that there is a pronounced increase in the EDNO formation in skeletal muscle during acute haemorrhage, which by its vasodilator action serves to counterbalance to a significant extent the concomitant reflex adrenergic vasoconstriction ( Mellander & Ekelund 1995, Ekelund & Mellander 1996). The increase in the EDNO production was graded in relation to the magnitude of the blood loss and the site of the EDNO vasodilator response was almost selectively located in the proximal arterial resistance (`feeder') vessels (25 μm).…”

“…The haemorrhage‐induced increase in the EDNO production in skeletal muscle seemed to be unrelated to neural mechanisms, shear stress or hypoxia ( Ekelund & Mellander 1996) and the observations rather suggested that some humoral factor, notably circulating catecholamines, might act as trigger for the increased EDNO production in bleeding. In view of previous in␣vitro studies ( Cocks & Angus 1983, Miller & Vanhoutte 1985, Angus et al .…”