Increase In Vasoconstriction Research Articles

Vasopressin V1 receptor‐mediated aldosterone production as a result of selective V2 receptor antagonism: a potential explanation for the failure of tolvaptan to reduce cardiovascular outcomes in the EVEREST trial

Plasma volume expansion in patients with heart failure (HF) is associated with neurohumeral activation; symptom and signs of pulmonary congestion and peripheral oedema; an increase in hospitalizations for HF; and cardiovascular mortality. A reduction in plasma volume, as evidenced by haemoconcentration, has recently been suggested to be associated with an improvement in cardiovascular mortality. However, while loop diuretics reduce plasma volume and relieve the symptoms and signs of pulmonary congestion, they activate the renin–angiotensin–aldosterone system (RAAS) and, in experimental studies and some, although not all, retrospective clinical studies have been associated with an increase in cardiovascular mortality. Due to the controversy associated with the use of high-dose loop diuretics and their effect on cardiovascular mortality in patients with HF and a reduced left ventricular ejection fraction (REF) there has been increasing interest in alternative and or supplemental diuretic strategies to reduce plasma volume and to improve cardiovascular outcomes in patients with HFREF. Tolvaptan, a selective V2 vasopressin antagonist, has been shown in pre-clinical and short-term studies in patients with HF to be a potent aquaretic with a resultant increase in urine output; a decrease in body weight; a decrease in pulmonary capillary wedge pressure; an increase in serum sodium concentration; without activation of the RAAS. However when studied over the longer term in patients with HFREF, it has not been shown to reduce natriuretic peptide levels or left ventricular remodelling, and did not improve cardiovascular outcomes despite an early improvement in symptoms of dyspnoea, a prolonged reduction in body weight, and normalization of serum sodium in hyponatraemic patients. The finding that tolvaptan failed to reduce natriuretic peptide levels and cardiovascular outcomes despite a reduction in body weight is especially notable since an increase in body weight post-discharge is the single most important predictor for readmission in patients with heart failure and a major predictor of mortality. The explanation for the failure of tolvaptan to improve ventricular remodelling, natriuretic peptide levels, and cardiovascular outcomes despite a reduction in body weight remains uncertain. Several explanations have, however, been proposed, including the suggestion that the dose of tolvaptan (30 mg/day) may have been inadequate; that patients selected for study did not have hyponatraemia; and the possibility that a reactive increase in vasopressin levels might over the long term stimulate the V1a receptor with a resultant increase in vasoconstriction, which might negate the beneficial effects associated with aquareses. Without further prospective mechanistic studies it is difficult to confirm or refute these explanations. Recently, however, it has been shown that a deficiency of the V1a receptor causes hyporeninaemic hypoaldsteronism, and stimulation of the V1a receptor causes the adrenal production of aldosterone. The V1a receptor also affects the renal tubular effects of aldosterone. We postulate that these findings may explain the paradox of a persistent reduction in body weight despite the lack of an improvement in natriuretic peptide levels and cardiovascular outcomes associated with the use of tolvaptan in EVEREST. This hypotheses and its implications for the therapy of patients with HF will be briefly discussed below. As noted above, V2 receptor antagonism results in a sustained reduction in body weight along with an early transient decrease in pulmonary capillary wedge pressure without activation of the RAAS. However, over the long term there is a reactive increase in vasopressin levels, with a resultant increased activation of the unprotected V1a receptor in the myocardium and vascular wall. This increase in vasopressin levels in patients receiving tolvaptan has recently been associated with an increase in aldosterone levels.

The Roles of Integrins in Mediating the Effects of Mechanical Force and Growth Factors on Blood Vessels in Hypertension

Hypertension is characterized by a sustained increase in vasoconstriction and attenuated vasodilation in the face of elevated mechanical stress in the blood vessel wall. To adapt to the increased stress, the vascular smooth muscle cell and its surrounding environment undergo structural and functional changes known as vascular remodeling. Multiple mechanisms underlie the remodeling process, including increased expression of humoral factors and their receptors as well as adhesion molecules and their receptors, all of which appear to collaborate and interact in the response to pressure elevation. In this review, we focus on the interactions between integrin signaling pathways and the activation of growth factor receptors in the response to the increased mechanical stress experienced by blood vessels in hypertension.

Phosphodiesterase Type 5 Inhibition

The development of right heart failure has been a clinical concern of physicians caring for patients after cardiac transplantation since the inception of the field.1 Although the problem of “fixed” pulmonary vasoconstriction that does not respond to the reduction of left ventricular filling pressure seems to have diminished since the early days of transplantation, there are still some patients in whom this remains a problem. Data from the International Society of Heart Transplantation Registry suggests that right ventricular (RV) dysfunction accounted for 50% of all cardiac complications and 19% of all early deaths among heart transplantation patients,2 with persistent pulmonary vasoconstriction a major contributing factor to early RV dysfunction. The cause of the increase in vasoconstriction is unknown, although it may be a result of humoral factors, including cytokines, promoting changes in vascular smooth muscle gene expression. The hallmark of this problem is a lack of sensitivity to endogenous and exogenous vasodilators, be they nitric oxide (NO) released from pulmonary vascular endothelium or exogenous agents acting through NO, endothelin, or prostaglandin signaling pathways.3 Heart failure patients with fixed pulmonary hypertension can be disqualified from consideration for transplant surgery, given their worse prognosis for early survival. One alternative for these patients is to attempt …

Modulation of aortic vascular reactivity by sex hormones in a male rat model of metabolic syndrome

Modulation by sex hormones of aortic reactivity in rats with the metabolic syndrome (MS) was investigated. The following groups of weanling male Wistar rats were used: control rats (C) received regular tap water while MS rats received 30% sucrose in their drinking water; both had rodent chow for 24 weeks. These two groups were further subdivided into the following four groups: intact (Int), castrated (Cas), castrated plus testosterone (T) and castrated plus estradiol (E). Vascular response of thoracic aortic rings to norepinephrine (NE), acetylcholine (ACh), indomethacin (Indo) and nitro-l-arginine-methyl ester (l-NAME) was investigated. Blood pressure (BP) and serum nitrates and nitrites were measured. BP and serum nitrates and nitrites were modified by castration and treatments with either T or E. Vasoconstriction in Int MS and Cas MS+T aortas was larger than in C and Cas C+T, respectively. Vasodilation in Int MS and Cas MS+T was reduced in comparison with C and Cas C+T, Cas MS and Cas MS+E. Indomethacin decreased vasoconstriction in all groups (P<0.002) but Int C and Cas C+T remained significantly smaller than Int MS and Cas MS+T. l-NAME in NE-contracted vessels induced a significant increase in vasoconstriction, except in Cas C+E rats; the responses of Int MS and Cas MS+T were significantly larger than in Int C and Cas C+T. The results suggest endothelial dysfunction in Int MS and Cas MS+T and a protective effect resulting from castration and castration plus E in MS animals, indicating a sex hormone influence.

Catecholamine therapy in cardiogenic shock: helpful, useless or dangerous?

Cardiogenic shock is characterized by inadequate organ and tissue perfusion, due to cardiac dysfunction, predominantly following acute myocardial infarction. Mortality rates for patients with cardiogenic shock remain high, ranging from 50-70 % despite effective therapy. Rapid diagnostics, aggressive therapeutic approach (invasive or surgical revascularisation) and pharmacological support are currently used to improve the clinical outcome and survival. In the first line commonly sympathomimetics like dopamine, dobutamine, epinephrine and norepinephrine are used for the pharmacological treatment. They have a high affinity for alpha- and beta adrenergic receptors, leading to a positive inotropic cardiac function, an increase in heart rate, oxygen enhanced demand, and an increase in vasoconstriction. However, there are also some disadvantages in the use of sympathomimetics in patients with cardiogenic shock. Clearly, metabolic acidosis due to the increased oxygen demand can be observed. Vasoconstriction induced by sympathomimetics can lead to perfusion mismatch or even deficit within the microcirculation. Additionally, in some studies which give evidence that the use of sympathomimetics can directly lead to enhanced systemic inflammatory response due to an increased IL-6 expression. However, sympathomimetics are still first line therapeutics for treatment of cardiogenic shock -- with respect to dosage and duration of treatment.

Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit

Objective The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model.Methods Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17β-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (Nϖ-nitro-L-arginine methyl ester), calcium and endothelin-1 were established.Results Treatment with MPA caused a significant increase in vasoconstriction, expressed as Emax (mN/mm, mean ± SEM; p < 0.05), in response to potassium (3.18 ± 0.19 vs. 2.47 ± 0.19) and calcium (4.00 ± 0.22 vs. 3.34 ± 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 ± 0.69 vs. 5.22 ± 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2.Conclusions In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.

Cardiac necrosis markers associated with low nitric oxide levels in the plasma of rabbits after treatment with vasopressin: protective effects of nitroglycerin administration

It has been reported that the administration of vasopressin induces myocardial ischaemia in rats, which causes electrocardiographic ST segment alterations according to many authors. But rat electrocardiogram (ECG) lacks ST segment. Consequently it appears important to study the effects of vasopressin in rabbits, which show ST segment present in the ECG. Since cardiac necrosis markers are released in the plasma of humans with myocardial infarction, as well as in a variety of experimental models of myocardial necrosis, it is possible that the same may occur in rabbits with myocardial ischaemia induced by vasopressin. The main aim of this study was to investigate whether the administration of vasopressin causes the appearance of specific myocardial necrosis markers, such as cardiac troponin I, myoglobin or creatine kinase MB (CK MB) in rabbits in the presence or absence of modified ECG profile, and to also verify whether these markers are associated with the alterations in some coagulation parameters, that are known to be induced by vasopressin. As the effects of vasopressin are counteracted by nitric oxide (NO), another aim was to verify whether vasopressin also affects plasma NO levels and whether the administration of a NO donor can reverse these effects. Vasopressin was administered to rabbits and caused ischaemic alterations such as electrocardiographic changes, and significantly increased the levels of plasma cardiac necrosis markers (c-troponin I, myoglobin and CK MB). It also elevated diastolic blood pressure (BP), lowered heart rate (HR), increased procoagulation activity, and lowered plasma NO levels. The appearance of heart necrosis, demonstrated by plasma cardiac necrosis markers in the animals receiving vasopressin, was attributed to a drug-induced increase in vasoconstriction and coagulation activity. The intense vasoconstriction and thrombosis may lead to endothelium necrosis and a consequent drop in NO production. The administration of the NO donor nitroglycerin (NG) in the vasopressin treated animals restored NO values, and was capable of preventing the appearance of the plasma cardiac necrosis markers and altered coagulation values. The protective activity of NG was attributed to NO release, which lowers BP values and counteracts coagulation activity in vasopressin-treated animals. The described procedure may also be proposed for the study of early ischaemic myocardial lesions and the screening of NO donors preventing myocardial damage.

The threshold and gain of thermoregulatory vasoconstriction differs during anesthesia in the dependent and upper arms in the lateral position.

Increased intraluminal pressure may help maintain vasodilation in a dependent arm even after hypothermia triggers centrally mediated thermoregulatory vasoconstriction. We therefore tested the hypotheses that the threshold (triggering core temperature) and gain (increase in vasoconstriction per degree centigrade) of cold-induced vasoconstriction is reduced in the dependent arm during anesthesia. Anesthesia was maintained with 0.4 minimum alveolar anesthetic concentration of desflurane in 10 volunteers in the left-lateral position. Mean skin temperature was reduced to 31 degrees C to decrease core body temperature. Fingertip blood flow in both arms was measured, as was core body temperature. The vasoconstriction threshold was slightly, but significantly, less in the dependent arm (36.2 degrees C +/- 0.3 degrees C, mean +/- SD) than in the upper arm (36.5 degrees C +/- 0.3 degrees C). However, the gain of vasoconstriction in the dependent arm was 2.3-fold greater than in the upper arm. Consequently, intense vasoconstriction (i.e., a fingertip blood flow of 0.15 mL/min) occurred at similar core temperatures. In the lateral position, the vasoconstriction threshold was reduced in the dependent arm; however, gain was also increased in the dependent arm. The thermoregulatory system may thus recognize that hydrostatic forces reduce the vasoconstriction threshold and may compensate by sufficiently augmenting gain. The threshold for cold-induced vasoconstriction is reduced in the dependent arm, but the gain of vasoconstriction is increased. Consequently, the core temperature triggering intense vasoconstriction was similar in each arm, suggesting that the thermoregulatory system compensates for the hydrostatic effects of the lateral position.

ENDOTHELIAL DYSFUNCTION AND HYPERTENSIVE VASOCONSTRICTION

A change in endothelial function is a common phenomenon in patients with essential hypertension and in animals with hypertension, whether primary or induced by a salt-rich diet. In hypertensive subjects, there may be a change in the synthesis, or the effect, of nitric oxide. Nevertheless, hypertensive vasoconstriction is at present associated, above all, with the degradation of this mediator by free radicals, such as the superoxide anion, released in the dysfunctional vascular endothelium. These radicals are also formed when hypoxanthine is turned into xanthine, and when the latter becomes uric acid, both having been catalysed by the enzyme xanthine oxidase. In physiological conditions, the concentration of superoxide radicals remains low within the organism as a result of its reaction with the superoxide dismutase enzyme. However, in pathological situations, such as arterial hypertension, there may be an increase in the production of these radicals or a deficiency of the superoxide dismutase enzyme. In hypertensive patients, the release of vasoconstrictor peroxides derived from the activity of cyclo-oxygenase in the endothelium and the vascular smooth muscle is also important. The excess free radicals released by the dysfunctional endothelium also stimulate the synthesis of these contracting agents. Moreover, it should not be forgotten that endothelin-1, which is similarly synthesized and released in the vascular endothelium, is the most powerful known endogenous vasoconstrictor. This peptide would therefore play a prominent part in some forms of hypertension. Although no changes in endothelin plasma levels have been found in essential hypertension, there may be an increase in its local concentration. It should be borne in mind that endothelin could strengthen the effect of other vasoconstrictors. Moreover, it may also provoke the release of free radicals and of cyclo-oxygenase-derived vasoconstrictor factors. The latest theories therefore indicate that the increase in vasoconstriction, which characterizes arterial hypertension, is associated with a greater production of free radicals. At the present time, antioxidant agents and xanthine oxydase-inhibiting compounds are being used to treat hypertension and other pathologies linked to endothelial dysfunction. In addition, it is thought that the therapeutic benefit of some anti-hypertensive drugs, such as calcium antagonists and angiotensin-converting enzyme inhibitors, could be in part due to the inhibition of the production of free radicals that they provoke. 1999 Academic Press@p$hr

Postischemic Left Ventricular Dysfunction Is Abolished by Alpha-Adrenergic Blocking Agents

Objectives. We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans.Background. The mechanisms underlying postischemic LV dysfunction are largely unknown.Methods. Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77 ± 5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 μg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 μg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline.Results. Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34 ± 9% to 45 ± 8% and to 49 ± 8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34 ± 6%), as in control subjects.Conclusions. LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

Role of extracellular UTP in the release of uracil from vasoconstricted hindlimb.

The source and function of elevated uracil release during vasoconstriction in the perfused rat hindlimb was investigated. The possibility that uracil release derived from the breakdown of released vasoactive uridine 5'-triphosphate (UTP) was examined. Exogenous UTP was found to be a potent vasodilator in the perfused rat hindlimb, opposing norepinephrine and angiotensin-induced increases in vasoconstriction and oxygen consumption. UTP was rapidly catabolized by the hindlimb to uridine 5'-monophosphate (UMP), uridine, and uracil, which were all devoid of vasoactivity. UTP was similarly catabolized by incubated rat aorta. Degradation of exogenous UTP by perfused hindlimb or aorta was inhibited by alpha, beta-methylene-adenosine 5'-diphosphate (AMP-CP), an inhibitor of ectonucleotidases. However, AMP-CP did not decrease uracil and uridine output by the hindlimb during angiotensin-mediated vasoconstriction and increased oxygen consumption. In particular, simultaneous infusion of AMP-CP with angiotensin did not increase efflux of UMP. Although exogenous UTP is a potent vasodilator in the perfused rat hindlimb, it appears not to be released intact during vasoconstriction. Hence, extracellular UTP is unlikely to be the precursor of the uracil release.

Age-related alterations in the arterial microvasculature of skeletal muscle.

This study investigated the possibility that the aging process results in alterations in the structure and/or functional reactivity of the microvessels that could contribute to increased resistance to blood flow in working skeletal muscle. Initially, latex casts were made of the cremaster muscle microvasculature in adult (12 mo) and senescent (24 mo) male Fischer 344 rats. Although the average diameter was not different between age groups, segmental length (distance between adjacent branches) increased significantly (3rd order) during aging. Additionally, in vivo experiments were performed to determine the response of the vessels to the topical application of norepinephrine and adenosine. There was no increase in vasoconstriction produced by norepinephrine; however, the vasodilation in response to adenosine declined dramatically (1st and 2nd order) with advancing age. It can be concluded that the increase in skeletal muscle vascular resistance during contraction in aged male rats could be explained by morphological changes and/or the diminished vasodilation elicited by adenosine.

Pathophysiological Role of the Vascular Smooth Muscle Cell

The vascular smooth muscle cell of the arterial media plays a predominant role in functional and structural alterations of the arterial wall in pathophysiological processes such as arterial hypertension, atheroma, or normal aging. The observed alterations are related to the three activities of the vascular smooth muscle cell, namely contractility, secretion of proteins from the extracellular matrix, and proliferation and migration. In arterial hypertension, vascular smooth muscle cells are functionally more contracted and structurally hypertrophic, and more collagen is secreted than under normal conditions. Similar structural changes are observed in the normal aging process. With respect to vascular smooth muscle cells, atheroma is characterized by their subintimal migration and proliferation, and by excessive excretion of collagen associated with other phenotypic modifications that are expressed in their regression to a myofibroblastic state. Regardless of the pathophysiological context, these phenotypic modifications of the vascular smooth muscle cell are always linked to an activation of the phosphoinositol pathways and to calcium accumulation. The activation of the phosphoinositol pathways seems to be a common feature of the different types of arterial hypertension. This activation can be associated with an increase in vasoactive peptides such as angiotensin II, vasopressin, or endothelin as in the secondary types of hypertension or directly related to an increase in vasoconstriction; or, as an exception, it can be spontaneously active in vivo and in vitro, as in the model of cultured vascular smooth muscle cells of the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral hemodynamics, blood viscosity, and the renin-angiotensin system in hemodialysis patients under therapy with recombinant human erythropoietin.

Treatment of renal anemia with rhEPO (120 U/kg body weight/hemodialysis) in transfusion-dependent patients on maintenance hemodialysis led to an increase in blood pressure, regional peripheral resistance and whole blood viscosity. Our results are in agreement with earlier findings that partial correction of renal anemia results in hemodynamic changes characterized by a fall in cardiac output together with an increase in blood pressure due to increased vascular resistance. The increase in whole blood viscosity correlated with the increase in regional peripheral resistance but not with the increase in mean arterial blood pressure. Thus, other regulating factors of vascular resistance must be involved. Correction of renal anemia does not influence the reninangiotensin system. However, peripheral responsiveness of vascular smooth muscles may have changed due to improved tissue oxygenation and thus leading to an increase in vasoconstriction.

Coronary hemodynamics and oxygen utilization after hematocrit variations in hemorrhage.

Twenty closed-chest dogs anesthetized with pentobarbital sodium were used for studying coronary hemodynamics and myocardial oxygen utilization during hemorrhagic hypotension, with the mean arterial pressure maintained constant at 50 mmHg. Variations of hematocrit (Hct) were achieved by exchange of blood with plasma or packed cells. Coronary blood flow (133Xe washout) varied inversely with Hct, whereas cardiac output (indicator dilution) showed a peak value at a Hct of approximately 25%. Coronary, systemic, and pulmonary flow resistances varied in the same direction with Hct, and the relationship was attributable to the change of blood viscosity with Hct. Analyses of vascular hindrance (= resistance/viscosity) suggested that during hemorrhagic hypotension, coronary vasodilation was maintained during variations of Hct. In systemic and pulmonary circulations, however, there were marked increases in vasoconstriction after hemodilution. The optimum Hct for maximum O2 transport was 25% for coronary circulatin and approximately 45% for systemic circulation. The O2 consumption (QO2) in the myocardium increased after hemodilution with a peak value at a Hct of approximately 25%. The QO2 in the total body was constant over a wide range of Hct between 25 and 45%, above and below which the QO2 decreased.

Vascular responses to temperature in the foot of the giant fulmar,Macronectes giganteus

1. Blood circulation to the leg of an antarctic bird, the giant fulmar,Macronectes giganteus, has been studied in response to changing the temperature of the ambient environment including immersion of the feet in ice water. 2. Measurements done include blood flow to the leg by an electromagnetic flow meter, blood pressure in the carotid artery and locally in a leg artery and vein, intravenous and arterial blood temperatures in the leg in addition to foot subcutaneous temperature and core temperature (deep pectoral temperature). 3. Blood flow to the lower leg varied between 10 ml/min and 40 ml/min during resting thermoneutral conditions. 4. Raising the core temperature by heating the central body increased foot blood flow to maximum values around 40 ml/min or 160 ml/min/100 g tissue. 5. Quick warming of the cold feet by immersion in hot water caused only slight increase in leg blood flow, whereas slow rewarming in air gave increasing leg blood flow when the local temperature of the foot increased from near zero to 35.6° C. 6. Sudden immersion of the foot in ice water (T = −2.0° C) elicited an immediate flow increase and a transient increase in foot arterial blood temperature. Venous pressure in the foot increased with blood flow while foot arterial pressure was unaltered. 7. The vasodilatation on ice immersion, termed the “cold flush” was followed by a gradual increase in vasoconstriction and reduced blood flow. After about 3 minutes fluctuations “huntings” appeared in leg blood flow and local temperatures in the foot. 8. The described circulatory changes are discussed in relation to thermal homeostasis of the bird and protection of the naked feet from cold shock and impairment of function on sudden cold exposure. Special reference is given to the phenomenon of cold vasodilatation earlier described on cold exposure of extremeties in mammals.