The pressure-flow relationship in the vascular bed of the skeletal muscle is depicted in Fig. 18.22. When there are abrupt changes in perfusion pressure from the control level, the flow rates obtained immediately after these changes are represented by the filled (red) circles. On the other hand, the steady-state flow rates obtained at the new perfusion pressure are represented by the open (blue) circles. These observations were redrawn from a study conducted by Jones RD and Berne RM in 1964.

From the pressure range of 20 to 120 mm Hg, it can be observed that the steady-state flow remains relatively constant. By calculating the hydraulic resistance across the vascular bed during steady-state conditions, it is revealed that the resistance vessels constrict with an increase in perfusion pressure and dilate with a decrease in perfusion pressure. Interestingly, this response to perfusion pressure is not dependent on the endothelium, as it is observed to be the same in intact vessels as well as vessels devoid of their endothelium.

According to the myogenic mechanism, the contraction of vascular smooth muscle occurs in response to an increase in the pressure difference across the blood vessel wall (transmural pressure), while relaxation occurs in response to a decrease in transmural pressure. The specific signaling mechanisms responsible for the contraction elicited by vessel distention are currently unknown. However, it is believed that stretch of vascular smooth muscle leads to an increase in intracellular calcium concentration, as demonstrated by previous studies. This suggests that an increase in transmural pressure activates membrane calcium channels.

Transient receptor potential (TRP) channels have been implicated in the myogenic mechanism. These channels are mammalian homologues of a gene found in Drosophila melanogaster. Mutations in this gene result in only a transient response to sustained light stimulus. The pressure-induced vasoconstrictive response of an artery, known as the myogenic response, follows a signal path involving pressure, increased phospholipase C activity, synthesis of diacylglycerol, activation of TRP channels, smooth muscle depolarization, and opening of L-type calcium channels. This ultimately leads to an increase in intracellular calcium concentration and muscle tone, thereby regulating vascular resistance. Other types of TRP channels have been proposed to participate in chronic hypoxic pulmonary hypertension and in the vasoconstriction caused by the α-adrenergic agonist norepinephrine.

Under normal conditions, blood pressure is maintained at a fairly constant level through the baroreceptor reflex. Therefore, the myogenic mechanism may have a minimal role in regulating blood flow to tissues. However, when an individual changes from a lying to a standing position, transmural pressure in the lower extremities increases, causing the precapillary vessels to constrict in response to this stretch.

Additionally, the endothelium that lines the vasculature produces various substances that can either relax (e.g., nitric oxide) or contract (e.g., angiotensin II and endothelin) vascular smooth muscle. Thus, the endothelium plays a crucial role in regulating blood flow to specific vascular beds.

Blood flow in a tissue is governed by its metabolic activity. In cases where there is inadequate oxygen supply, the tissue releases vasodilator metabolites, which act locally to dilate the resistance vessels. When the tissue's metabolic rate increases or its oxygen delivery decreases, the release of vasodilator substances is further enhanced.
•Fig. 18.22 Pressure-flowrelationshipinthevascularbedoftheskeletalmuscle.Filled (red) circles representtheflowratesobtainedimmediatelyafterabruptchangesinperfusionpressurefromthecontrollevel(thepointwherelinescross).Open (blue) circles representthesteady-stateflowratesobtainedatthenewperfusionpressure.(RedrawnfromJonesRD,BerneRM.Circ Res. 1964;14:126.)0 20 40 60 10080 120 140 160 180 0 2 4 6 8 10 12 Perfusion pressure (mm Hg) Muscle blood flow (mL/min/100 g)
Over the pressure range of 20 to 120 mm Hg, the steady-state flow is relatively constant. Calculation of hydraulic resistance (pressure/flow) across the vascular bed during steady-state conditions shows that the resistance vessels constrict with an elevation in perfusion pressure but dilate with a reduction in perfusion pressure. This response to perfusion pressure is independent of the endothelium because it is identical in intact vessels and in vessels that have been stripped of their endothelium. According to the myogenic mechanism, vascular smooth muscle contracts in response to an increase in the pressure difference across the wall of a blood vessel (transmural pressure), and it relaxes in response to a decrease in transmural pressure. The signaling mechanisms that allow distention of a vessel to elicit contraction are unknown. However, because stretch of vascular smooth muscle has been shown to raise intracellular [Ca++], an increase in transmural pressure is believed to activate membrane calcium channels.
Transientreceptorpotential(TRP)channelshavebeenimplicatedinthemyogenicmechanism.ThesechannelsaremammalianhomologuesofaDrosophila melanogaster genethat,whenmutated,allowsonlyatransientresponsetoasustainedlightstimulus.Thepressure-inducedvasoconstrictiveresponseofanartery(myogenicresponse)appearstohavethefollowingsignalpath:pressure → increasedphospholipaseCactivity→ synthesisofdiacylglycerol→ activationofTRPchannel→ smoothmuscledepolarizationandopeningofL-typecalciumchannelsthatincreaseintracellular[Ca++]andmuscletone.Thisisameansofregulatingvascularresistance.OtherTRPchanneltypeshavebeenproposedtoparticipateinchronichypoxicpulmonaryhypertensionandinthevasoconstrictioncausedbytheα-adrenergicagonistnorepinephrine.
In normal subjects, blood pressure is maintained at a fairly constant level via the baroreceptor reflex. Hence, the myogenic mechanism may play little role in regulating blood flow to tissues under normal conditions. However, when a person changes from a lying to a standing position, transmural pressure rises in the lower extremities, and the precapillary vessels constrict in response to this imposed stretch.
, the endothelium lining the vasculature produces a number of substances that can relax (e.g., nitric oxide) or contract (e.g., angiotensin II and endothelin) vascular smooth muscle. Thus the endothelium plays an important role in regulating blood flow to specific vascular beds.
The metabolic activity of a tissue governs blood flow in that tissue. Any intervention that results in inadequate O2 supply prompts the formation of vasodilator metabolites that are released from the tissue and act locally to dilate the resistance vessels. When the metabolic rate of the tissue increases, or when O2 delivery to the tissue decreases, more vasodilator substances are released (see
Chapter 17).