Review

Veins and venous tone☆

Venous capacitance plays an important role in cardiovascular homeostasis. The anatomical loci within the central nervous system involved in modulating venous function remain to be elucidated. Stimulation of the hypothalamic paraventricular nucleus is known to increase sympathoadrenal outflow and arterial blood pressure. The present study was undertaken to determine whether electrical stimulation of the paraventricular nucleus can also affect the venous circulation. Mean circulatory filling pressure (MCFP) was used as an index of venous tone. Male Long Evans rats were initially anesthetized with pentobarbital (i.p.; 60 mg/kg) and subsequently maintained with urethane (i.v.; 600 mg/kg). Blood pressure and systemic venous pressure were monitored via catheters in the femoral artery and vein and heart rate eas derived from the pulsatile blood pressure signal. A latex tipped balloon was placed in the right atrium via the right jugular vien. Mean circulatory filling pressure was calculated from the arterial and venous plateau pressures recorded during five second balloon inflations. Arterial pressure, systemic venous pressure, heart rate and mean circulatory filling pressure were monitored before and during unilateral monopolar electrical stimulation (0.5 ms pulses at 50 Hz for a train duration of 10 s with constant current intensities of 100, 150, 200, and 300 μA) of the paraventricular nucleus. Increased graded stimulation of the paraventricular nucleus increased blood pressure by 6 ± 2, 8 ± 1, 13 ± 2 and 26 ± 5 mm Hg while heart rate changed by −22 ± 6, −18 ± 6 and −15 ± 9 bpm and+10 ± 10 bpm, respectively. Moreover, graded increases in MCFP of 0.64 ± 0.09, 1.04 ± 0.21, 1.19 ± 0.11 and 1.50 ± 0.25 mm Hg were observed concurrently. The results demonstrate, for the first time, that in addition to the documented effects on the arterial circulation, stimulation of the paraventricular nucleus induces systemic venoconstriction.

Effects of pulsatile and nonpulsatile perfusion on capacity system were investigated in 33 open-chest mongrel dogs with extracorporeal circulation. In 28 dogs with intact carotid sinus nerves, after changing from nonpulsatile to pulsatile systemic perfusion the mean arterial pressure decreased by 14 ± 1.5 mm Hg, peripheral resistance by 423 ± 15 dyne · cm^–5 · sec, and venous blood volume by 3.3 ± 0.4 ml/kg. After changing from pulsatile perfusion to nonpulsatile systemic perfusion the mean arterial pressure increased by 15 ± 2.2 mm Hg, the peripheral resistance by 431 ± 15 dyne · cm^–5 · sec, and venous volume by 3.9 ± 0.5 ml/kg. The same effects were observed in five dogs with bilateral isolated carotid pulsatile perfusion or nonpulsatile perfusion and systemic nonpulsatile perfusion. These effects were abolished after denervation of pressor receptors and pharmacologic blockade of α and β receptors. It is proposed that with nonpulsatile perfusion carotid sinus-mediated vasoconstriction occurs in the downstream part of the capacitive system, where more pronounced wall musculature with increased number of adrenergic receptors is present. The throttle effect caused by this “resistance” part of venous circulation leads to increase of pressure in the upstream section of the capacitive system, compensates for the constrictive effect of the sympathetic tone, and leads finally to an increased volume of the capacity system. We conclude that venous response to different perfusion modalities is critically dependent on intact carotid sinus nerves and adrenergic receptors in the veins.

The effect of cardiopulmonary bypass on venous tone was evaluated in 19 patients undergoing coronary artery bypass graft operations. The use of cardiopulmonary bypass with reduction of mean arterial pressure, nonpulsatile blood flow, and emptying of the heart maximally stimulates the sympathoadrenal system and would be expected to cause intense venous constriction. Venous capacitance, however, was reduced by the general effects of the operation, including anesthesia and surgical trauma, while cardiopulmonary bypass was a minor factor in the venous constriction response.

Vasomotor dynamics were studied in 52 patients undergoing direct coronary revascularization or mitral valve replacement utilizing cardiopulmonary bypass. Emphasis was placed on the study of venous tone. Operation resulted in a general vasoconstrictive response with increased arterial resistance and reduced venous capacitance. These changes were magnified in patients who underwent mitral valve replacement for mitral valve stenosis related or partially related to reduced cardiac performance before and after operation. Nine patients became hypertensive following coronary artery bypass and were treated with nitroprusside; eight patients were given nitroglycerin to reduce venous tone and prevent hypertension. A comparison of these two vasodilators, with their somewhat different actions on the vascular bed, reveals that afterload reduction and increase of cardiac output were equivalent with both. However, nitroglycerin had the effect of increasing venous capacitance, while nitroprusside had little effect on the venous circulation. In addition, nitroglycerin was especially effective in reducing venous tone and left ventricular preload following mitral valve replacement. Relative merits of pharmacologic reduction of venous tone as a part of overall relief of increased vascular resistance following cardiac operation should be considered when attempting to obtain an optimal hemodynamic state.

Oral administration of methyldopa (100 mg/kg, twice daily for 3 days) to mongrel dogs produced a significant decrease in blood pressure and heart rate. The drug treatment affected neither the resting venous tone nor the cardiac output. Thus, the hypotensive effect of the drug was predominantly due to a reduction in total peripheral resistance.

Vasoconstrictor responses of the renal vasculature to sympathetic nerve stimulation were significantly impaired after methyldopa at all the frequencies, while mesenteric vasoconstrictor responses to sympathetic nerve stimulation were impaired only at the lower stimulation frequencies. In addition, methylnorepinephrine was a significantly less potent vasoconstrictor than norepinephrine in the renal vasculature, but was equipotent to norepinephrine in the mesentery. The finding of a reduction in the renal vascular resistance of methyldopa-treated dogs, with no such alteration in the mesenteric vascular resistance, is consistnet with the nerve stimulation studies. Therefore, the results of the present investigation indicate that in addition to the existing evidence favoring a central site of action for methyldopa, the impairment of peripheral sympathetic neuronal function is also of importance in accounting for the hemodynamic alterations observed following treatment with methyldopa.