David L. Wiegman

Anesthesia-induced alteration of small vessel responses to norepinephrine

Closed-circuit television microscopy was used to quantitate the in vivo response of small arteries (approximately 100 micron) and small veins (approximately 150 micron) to topically applied norepinephrine in the rat cremaster muscle. Rats were anesthetized with pentobarbital (50 mg/kg), or urethane (1200 mg/kg) or a combination of urethane (800 mg/kg) and chloralose (60 mg/kg). Complete concentration-response curves were obtained for an artery and vein pair in each rat and pD2 values (-log ED50) were used to evaluate the vascular sensitivity to norepinephrine. Both the artery and the vein in urethane-anesthetized animals had decreased sensitivity to norepinephrine in comparison to the vessels of animals anesthetized with pentobarbital or urethane-chloralose. Pretreatment with cocaine (10(-5) M) significantly increased the sensitivity of both the artery and vein in pentobarbital-anesthetized animals but did not affect the vessels in urethane-chloralose-anesthetized animals. These results are consistent with two opposing effects of the urethane-chloralose combination. The first is an increased sensitivity to norepinephrine via blockade of neuronal uptake and the second is a decreased sensitivity of norepinephrine via a vascular inhibitory effect of urethane.

Effects of vasodilators and peritoneal dialysis solution on the microcirculation of the rat cecum.

Summary Peritoneal dialysis solutions produce vasodilation of small arteries and veins on the mesothelial surface of the rat cecum. Dilation in the artery is not altered by the addition of nitroprusside to the dialysis solution. However, there is a dramatic increase in dilation of the small vein upon addition of nitroprusside. This small vein phenomena is not unique to nitroprusside since papaverine can produce dilation of equal magnitude. However, of the three vasodilators tested (nitroprusside, papaverine, and isoproterenol), at comparable vein dilation, nitroprusside produced the greatest small artery dilation. Thus, a unique combination of small vein and small artery mechanisms may in part explain the increases in clinical clearances observed with the addition of nitroprusside to dialysis solution.

Modification of α-adrenergic responses of small arteries by altered PCO2 and pH

Closed-circuit television microscopy was used to measure in vivo small artery (75–140 μ) and vein (105–230 μm) diameters to determine if changes in tissue PCO2 and/or pH would alter the microvascular responses to norepinephrine. Sprague-Dawley rats were anesthetized with a combination of urethane (800 mg/kg) and α-chloralose (60 mg/kg). The cremaster muscle with intact circulation and inervation was suspended by sutures in a 60-ml bath which contained and mofified Krebs solution (31°C) that was buffered by Tris of bicarbonate. There were four groups of animals with different combintions of bath PCO2 and pH: (1) PCO2 < 10 mm Hg and pH = 7.2, PCO2 < 10 mm Hg and pH = 6.9, (3) PCO2 = 60–70 mm Hg and pH = 6.9. The maximal responses of the small artery and vein to norepinephrine were similar for the four groups. The artery sensitivity to norepinephrine was signficantly lower for group 4 when compared to groups 1, 2 and 3, but there was no effect on small vein sensitivity. This, the combination of decreased pH and increased PCO2 reduces small artery sensitivity to norepinephrine in the cremaster muscle of the rat.

Peritoneal Clearances with Three Types of Commercially Available Peritoneal Dialysis Solutions

Peritoneal clearances were measured in multiple patients with different types of peritoneal dialysis solution to assess the effects of pH, choice of buffer anion (acetate versus lactate), and the effects of nitroprusside (a vasodilator) in combination with different buffer anions and varying pH. The studies show no differences in peritoneal clearances at very low solution pH (less than 6 as is commonly available) as compared to a pH nearer to 7 or above. There were no differences between solutions with acetate as compared to those with acetate. Nitroprusside significantly increased clearances in all solutions to a similar extent.

Neurohumoral Control of Blood Vessels

Renkin and Rosell (1962) reported specific sites for eNS control of arterioles and precapillary sphincters. Gootman et al. (1973) showed that all segments of precapillary microvessel and sphincter can respond to eNS stimulation. However, precapillary arterioles (metarterioles) and precapillary sphincters failed to respond to supramaximal stimulation of paravascular nerves in rat mesentery (Furness and Marshall, 1974). In the present experiment, responses of the larger consecutive segments of arterioles (Art) were measured during electrical stimulation of vasoactive eNS sites in nine rats with chronically implanted unipolar electrodes. Currents were for maximal constriction or lumen closure of precapillary sphincter (Pc sph) and/or immediately preceding metarteriole (Met): 0.08–0.15 mA (10- strains, 100-μs pulses 5–100 Hz). Under pentobarbital sodium (25 mg/kg, i.m.), responses of microvessels were measured by image-splitting methods in mesoappendix in six rats,cremaster in two rats, and both in one. In all experiments, stimulation resulted in blood pressure elevation (112.6 ± 17.6% to 165.2 ± 18.5% mm Hg, mean and standard deviation) and constriction of three consecutive segments of precapillary vessels and sphincter: 10.5 ± 9.3% for Artl (43.4 ± 8.8 μm, ID), 40.0 ± 26.6% for All (20.4 ± 3.7 μm, ID), 70.3 ± 24.6% for Met (11.4 ± 3.7 μm, ID), and 75.5 ± 20.2% for Pc sph (7.5 ± 1.3 μm, ID). Stimulation characteristically increased (×3) vasomotor activity of Pc sph and Met, but infrequently increased that of larger arterioles at currents used.

In vivo Venular Changes with the Development of One-Kidney, one-Clip Hypertension in the Rat

Television microscopy was used to quantify in vivo resting venular diameters and the responses to topically applied norepinephrine in the cremaster muscle of two groups of urethanchloralose anesthetized rats: normotensive rats (NT) and one-kidney, one-clip Goldblatt hypertensive rats (1K1C). Observations were made two weeks after the surgery which was used to induce renovascular hypertension. At this stage, we have previously observed an increase in arteriolar reactivity (1). In the current study, mean arterial blood pressures for 1K1C (149 +/- 5 mmHg) were significantly higher than pressures for NT (102 +/- 3 mmHg). Venules were categorized by branching order and venular diameters were measured at three different levels of the microcirculation: first (1V), second (2V), and third order (3V) venules. Reactivity to norepinephrine at all venular levels in the 1K1C group was similar to that recorded for the NT group. Resting venular luminal diameters, however, were significantly smaller (20%) for large (1V) venules of the HT group (137 +/- 9 micron) compared to those for the NT group (171 +/- 10 micron). Thus, in contrast to previously reported data for arterioles, a structural venoconstriction and not an increase in venular reactivity appears to characterize the early vascular changes associated with this form of renovascular hypertension.

Calcium Modulation of Microvascular Sensitivity during Renovascular Hypertension

Abstract The effects of in vivo alterations in local calcium concentration on small vessel responses to norepinephrine were obtained for a first order arteriole and venule in the cremaster muscle of normotensive and one-kidney, one-clip Goldblatt hypertensive rats. The cremaster with intact circulation and innervation was suspended in a modified Krebs solution which contained either 1.3, 2.6, or 5.1 mM CaCl2. Closed-circuit television microscopy was used to measure vessel diameters. The resting lumenal diameters of first-order arterioles in hypertensive rats were 31% smaller than lumenal diameters of the corresponding arterioles in normotensive rats. Concentration-response curves showed that the norepinephrine sensitivity (pD 2) of first-order arterioles in normotensive rats was significantly increased by a change in bath [Ca2+] from 1.3 to 2.6 mM; however, the norepinephrine sensitivity of comparable arterioles in hypertensive rats was not affected by this change in bath [Ca2+]. These data indicate that mechanisms for calcium modulation of vasoconstriction are attenuated for large arterioles in the cremaster muscle of one-kidney, one-clip Goldblatt hypertensive rats.