J. P. Gilmore

The Mechanism of Adaptation of Left Atrial Stretch Receptors in Dogs with Chronic Congestive Heart Failure

Chronic congestive heart failure (CHF) was induced in dogs by the construction of an aorto-caval fistula below the level of the renal arteries. Aorto-caval fistula dogs showed signs of CHF which included ascites, hind limb edema, and pulmonary congestion. Ventricular catheterization indicated a significantly higher left ventricular end diastolic pressure and lower maximum velocity of left ventricular pressure development/left ventricular end diastolic pressure in CHF dogs when compared to sham-operated controls. Heart weight/body weight ratios were significantly higher in CHF dogs. Electrophysiological recordings from medullated left atrial type B receptors from the cervical vagus indicated a depressed sensitivity of these receptors in CHF dogs when compared to sham-operated control dogs. For any given change in left atrial pressure, the discharge of left atrial receptors was significantly reduced in CHF dogs compared with sham-operated controls. The mechanism for this depressed sensitivity was investigated. Sonomicrometry of the left atrial appendage indicated a decreased compliance of the left atrial appendage in the dogs with chronic CHF. In addition, microscope examination of the complex unencapsulated receptor endings taken from the left atrial endocardium indicated a marked alteration in receptor morphology. A loss of the end arborization was the most typical finding. It is concluded that chronic CHF brought about by an aorto-caval fistula results in a depressed left atrial stretch receptor response and that both decreased left atrial compliance and structural alterations in the receptor endings may account for this depressed sensitivity.

Direct evidence for myogenic autoregulation of the renal microcirculation in the hamster.

We transplanted neonatal hamster renal tissue into a hamster cheek pouch chamber and subjected the renal tissue to increases and decreases in extravascular pressure. A decrease in extra-vascular pressure decreased, and an increase in extravascular pressure increased, the diameter of preglomerular arterioles. Thus, the change in preglomerular arteriolar diameter was directly related to alterations in extravascular pressure. Neither saralasin nor indomethacin affected these changes, whereas papaverin prevented them. The efferent arterioles responded passively to changes in extra vascular pressure; i.e., the changes in their diameter were inversely related to changes in extravascular myogenic autoregulation of preglomerular vessels. CircRes 47: 226-230, 1980

Natriuretic activity of human and monkey atria.

Recent evidence indicates that mammalian atria contain a substance that produces a rapid onset natriuresis in anesthetized rats. In the present experiments, small portions of human right atria obtained from patients undergoing coronary bypass surgery, as well as monkey atria and ventricles obtained from the Regional Primate Center, Seattle, were boiled or acid extracted and lyophilized. These materials (30 μg/kg) were dissolved in Ringers lactate and injected intravenously into anesthetized monkeys to determine their effects on renal function. Their effects were also compared with those of furosemide (0.1 μg/kg) and chlorothiazide (10 μg/kg). Human and monkey atrial extracts produced significant increases in sodium and calcium excretion that were independent of changes in creatinine clearance. Monkey ventricular extract had no consistent renal effects. Furosemide, but not chlorothiazide, mimicked the renal responses to human and monkey atrial extracts in terms of time of onset, duration, and pattern of electrolyte excretion. These data suggest that primate atrial tissue contains a heat- and acid-stable natriuretic factor similar to that first described in the rat, suggesting that mammalian atrial natriuretic factors are cross-reactive among species. In addition, atrial natriuretic factors may have a mechanism of action similar to that of furosemide.

The selective response to adenosine of renal microvessels from hamster explants

The present study was undertaken to investigate the effect of adenosine on the microvasculature of the hamster kidney and the possibility of angiotensin II mediation. Renal tissue from neonatal hamsters was grafted into the cheek pouch of 33 adult hamsters. Seven to twelve days later the renal microcirculation was studied. Adenosine was tested on the pre- and postglomerular arterioles as well as on cheek pouch arterioles before and after applying an AII antagonist, saralasin. Adenosine dilated the cheek pouch arterioles and constricted the preglomerular arterioles in a dose-dependent manner. Adenosine had no effect on postglomerular arterioles. The renal vasoconstriction persisted as long as adenosine was present. Theophylline reduced the adenosine-mediated vasoconstriction of the afferent arteriole in a dose-dependent manner. These changes were not altered in the presence of saralasin at various doses, one of which was 20-fold greater than that required to abolish the vasoconstrictor response of a test dose of angiotensin II. This study indicates that the adenosine-mediated vasoconstriction of the preglomerular microvessels is not mediated via the renin-angiotensin system but may be a direct effect of adenosine.

Microvascular pressure distribution and responses of pulmonary allografts and cheek pouch arterioles in the hamster to oxygen.

Despite extensive investigations of the pulmonary circulation using both in vitro and in vitro preparations, few direct microcirculatory studies have been made. Consequently, the mechanisms involved in the response of the pulmonary microvasculature to changes in oxygen tension remain unclear. The present study represents the first direct observation of the responses in pulmonary microvessels to alterations in oxygen tension. Neonatal lung tissue was transplanted into the hamster cheek pouch using a chamber technique. Both tissues were characterized with respect to their microvascular pressure profile and vascular response to hypoxia. The results showed the two tissues to be remarkably different. Small pulmonary and cheek pouch arterioles exhibited opposite responses to changes in oxygen environment; hypoxia elicited a constriction of pulmonary arterioles, but a dilation of cheek pouch arterioles. Pulmonary capillary pressure, although comparable to that measured in the intact lung (13 mm Hg), was substantially lower than cheek pouch capillary pressure, which was within the range of that described for several systemic vascular beds. The microcirculatory effects of oxygen on both tissues were confined to the arteriolar segments. The characteristics of this pulmonary microcirculation are such that it is a unique model for further physiological and pharmacological studies.

Intravascular pressure distribution and dimensional analysis of microvessels in hamsters with renovascular hypertension

Abstract Microvascular pressures and dimensional analysis (wall and lumen diameters) were measured in the branching network of arterioles and venules in the cheek pouch of both normotensive (NT) and hypertensive (HT) hamsters before and after vasodilating with nitroprusside (10 −4 M ). The Grollman technique was used to induce renovascular HT in 15 hamsters and 12 others were sham operated. The microcirculation of the cheek pouch was evaluated 10–26 days later using intravital microscopy after anesthetization with pentobarbital. Systemic blood pressure (direct catheterization) and microvascular pressure (Servo-Null system with micropipets) were measured. In the HT hamsters (133 ± 3 mm Hg), all arteriolar microvascular pressures were increased by 15–26% as compared to the NT hamsters (113 ± 4 mm Hg). However, pressures in small venules (10–20 μm) were decreased by 50–60%. Lumen diameters in first-order arterioles (90–120 μm) and in the venules of HT hamsters decreased. Vasodilation reduced systemic and microvascular pressures and increased lumen diameters to the same extent in both NT and HT hamsters. These results indicate that in HT hamsters arteriolar pressures are elevated and that there is a large drop in pressure across the capillaries which includes small arterioles and venules. These elevated arteriolar pressures do not appear to be due to structural hypertrophy with encroachment on lumen diameters.

Discharge of type B atrial receptors during changes in vascular volume and depression of atrial contractility

1. Single unit recordings from type B atrial receptors were obtained from slips of the left cervical vagus nerve during acute increases and decreases in atrial pressure produced by infusion of isotonic saline and withdrawal of blood.

Responses of pulmonary allograft and cheek pouch arterioles in the hamster to alterations in extravascular pressure in different oxygen environments.

The responses to changes in trangmural pressure were investigated in pulmonary allo-graft and cheek pouch arterioles in two oxygen environments. Neonatal hamster lung tissue was transplanted into adult hamster cheek pouches. After vasculaxization (8–10 days), pulmonary and cheek pouch vessels were observed by intravital microscopy in hamsters anesthetized with pentobarbital. By gassing the suffusion solution (bicarbonate-buffered Ringers) (pH 7.4 at 35–37°C) with either low oxygen (95% N2/6% CO2) or high oxygen (75% N2/5% CO2/20% O2) and after sealing the top of the chamber, extravascular pressure was altered by varying the fluid volume of the closed chamber. Changes in arteriolar diameters in response to positive and negative square-wave pressure pulses were quantified using a video micrometer and close-circuit TV system. Pulmonary arterioles showed a passive dilation or constriction in response to increases or decreases in transmural pressure (±20 mm Hg). These responses were not altered either by changes in Po2 or nitroprusside. In contrast, cheek pouch arterioles showed myogenic responses by constricting when transmural pressure was increased and vice versa. These responses were potentiated at high Po2 and abolished with nitroprusside. It is concluded that a myogenic response is dominant in cheek pouch arterioles but not in pulmonary arterioles under these conditions. These latter observations are consistent with results obtained from isolated, intact lung.

Differential response of hamster cheek pouch microvessels to vasoactive stimuli during the early development of hypertension.

Arteriolar responses in the hamster cheek pouch to direct microapplications of norepinephrine (NE), angiotensin n (A II), and potassium chloride (KC1) were investigated during the early developmental phase of hypertension. After determination of arterial pressure in 12 hamsters, control luminal and wall diameters and the response of arterioles (second order branching, 28-60 jun diameters) to microapplications of NE (0.5, 1.0, 5.0 ng), A II (0.5 ng), KC1 (22.2 min) and the vehicle (Tris-buffered Ringers solution) were determined. Then using a figure-eight ligature around each kidney hypertension was induced in nine animals, and three were sham-operated. Measurements were repeated on the same hamsters 4, 8, and 13 days later. Four of the nine animals developed a sustained hypertension (HT-S) and the remaining five developed a transient hypertension (HT-T), only on day 4. The sham-operated hamsters remained normotensive. The arteriolar response to KC1 was increased significantly in the HT-S group on days 4 and 8 whereas the arteriolar response to NE and A II was increased significantly on days 8 and 13. There were no significant differences in the arteriolar responses of either the HT-T or normotensive group to any agent at any time. Futhennore, there were no significant changes in arteriolar wall/lumen ratios for any group at any time. Thus, the transient nature of the arteriolar response to potassium combined with the delayed Increase in the arteriolar response to NE and A II implies that there are two vascular phases associated with the early development of hypertension in this model. The first phase may be an ionic alteration which in turn may initiate the second or humoral phase. Ore Res 44: 512-517, 1979

Failure of left atrial distension to alter renal function in the nonhuman primate

Experiments were undertaken to determine the influence of increasing left atrial pressure on renal function in the nonhuman primate. Significant elevations of left atrial pressure, produced by using an intra-atrial balloon, had no effect on salt or water excretion, renal plasma flow, or glomerular filtration rate. There were no significant changes in heart rate or blood pressure. We conclude that, unlike those in the dog, atrial receptors in the nonhuman primate play little or no role in modulating salt and water excretion.