Continuous measurement of renal cortical blood flow and renal arterial blood flow during stimulation of the renal nerve

Stimulation of the renal sympathetic nerve in young pigs with biphasic pulses of current (3 mA, 800 microseconds per phase, 5, 10 and 50 Hz) produced decreases in arterial and cortical blood flow in the kidney, with the greatest decreases occurring at the highest stimulus frequencies. The decrease in cortical flow lagged that in arterial flow by 1.53-1.99 s; the delay increased with decreasing frequency but was unaffected by captopril, an angiotensin-converting enzyme-blocking agent. This result was consistent with the hypothesis that stimulation of the sympathetic nerve causes constriction first in the afferent arteriole and then in the efferent arteriole. Systemic arterial pressure increased during stimulation of the nerve; the increase was greater in intact nerves than in nerves that had been crushed proximal to the point of the stimulus, indicating that pigs do have renal afferent nerves. Pressure increased after the stimulus ended, but the increase abated or changed to a decrease after administration of captopril. The changes in flow were unaffected by administration of captopril, but were markedly reduced by the blocking agent labetalol (renal arterial flow, 77 +/- 14 per cent; cortical flow, 70 +/- 12 per cent). Thus, the observed changes in flow resulted from direct stimulation of the sympathetic nerves and not from stimulation of the renin-angiotensin system, which affects the pressure response after the stimulus.     

Effect of vasoactive intestinal polypeptide on cerebral blood flow in the goat

The effect of vasoactive intestinal polypeptide (VIP) on the cerebral blood flow was investigated in the goat. An electromagnetic flow probe was placed around the internal maxillary artery for continuous measurement of ipsilateral blood flow. Intraarterial injection of VIP resulted in a dose-dependent increase in the cerebral blood flow. The effect was not antagonized by any of the antagonists atropine, propranolol, phentolamine and naloxone administered intraarterially 1 min before VIP. It is discussed that VIP may play a physiological role in the local blood flow regulation in the CNS.     

Intramyocardial distribution of blood flow in hemorrhagic shock in anesthetized dogs.

In 34 anesthetized, open-chest dogs aortic blood pressure was kept at 35-40 mmHg for 3 h to determine if maldistribution of coronary blood flow (CBF) could contribute to the irreversibility of hemorrhagic shock. Six dogs were pretreated with phenoxybenzamine (PBZ) and 11 dogs (3 with PBZ) received hypertonic mannitol infusions in late hemorrhage. Changes of heart rate, cardiac output, and peripheral resistance were similar to those described by others. In untreated dogs total and left ventricular CBF fell, as did coronary vascular resistance. However, minimal coronary resistance after transient ischemia rose progressively and the ratio of subendocardial:subepicardial flow fell, as did the percentage of diastolic coronary flow. Mannitol infusion returned CBF and steady-state and minimal postischemic coronary resistance to control values and also returned to normal the increased myocardial water content found in late hemorrhage. Phenoxybenzamine delayed but did not prevent the rise of coronary vascular resistance or decreased subendocardial flow. These studies suggest that there may be subendocardial ischemia, possibly due to myocardial edema, in hemorrhagic shock.     

Distribution of renal blood flow in dogs with congestive heart failure.

Studies were performed to determine whether the intrarenal distribution of cortical blood flow is altered in congestive heart failure. Utilizing the radioactive microsphere method, we studied eight dogs that developed congestive heart failure secondary to the construction of an aortocaval fistula. They had marked reduction in total renal blood flow not accompanied by intracortical redistribution of blood flow. All dogs had developed edema and/or ascites, and gained a mean of 3.4 kg; glomerular filtration rate, hematocrit, and urinary sodium excretion fell significantly. Renal vascular resistance increased; mean blood pressure and filtration fraction were unchanged. Furosemide was administered to a second group of nine fistula dogs. The drug produced a marked natriuresis associated with a decrease in outer cortical blood flow (zone 1) and an increase in midcortical zones 2 and 3; no change was observed in zone 4. We conclude: 1) chronic salt retention occurs in high-output heart failure in the absence of redistribution of renal cortical blood flow, and 2) the effect of furosemide on intrarenal hemodynamics of dogs with heart failure is similar to that seen in normal animals.     

Atriopeptins and renal cortical and papillary blood flow

Studies were made of the effect of two pure synthetic atrial natriuretic factors (ANF) on renal cortical and papillary blood flow and on the excretion of sodium, potassium and water in young Munich Wistar rats by means of laser-Doppler flowmetry. The effects of Atriopeptin I (AP I), which selectively relaxes intestinal smooth muscle, were compared with those of Atriopeptin II (AP II), which relaxes both vascular and intestinal smooth muscle. Both peptides were administered by continuous intravenous infusion at 10 μg h^-1 kg^-1 body wt after a control period. A time control group was studied in parallel to see whether the variables investigated varied with time. In rats receiving vehicle alone (time control) and in those receiving AP I, there was no significant change either in the cortical or papillary blood flow, or in blood pressure (BP). The AP II infusion resulted in an increase in blood flow which was only transient despite the continous infusion. Cortical blood flow increased by 22% (peak value) and papillary blood flow increased by 95% (peak value). The blood pressure (BP) decreased by 12% to a steady state level (103 ± 2 vs. 91 ± 2 mm Hg). The AP I caused a steady two-fold increase in sodium excretion (U_NaV), a 35 % increase in potassium excretion (U_KV) and an 85% unsient increase in urine flow rate (V). Infusion of AP II resulted in a more than 60-fold increase in U_NaV during the period of increased blood flow, and then reached a steady state level 10 times higher than the control value. The U_KV increased four-fold and then reached a steady state level 60% above the control value. The urine flow rate showed a 10-fold increase and then reached a steady state level 85% above the control value. In conclusion, AP I and AP II appear to increase solute excretion predominantly by affecting tubular transport mechanisms. The AP II, through its vascular effects, will transiently increase renal blood flow, preferentially in the inner medulla, and presumably the glomerular filtration rate (GFR), which in turn will contribute to the natriuretic response.,     

Cutaneous blood flow measurements: A standardization of the microsphere assay for vasoactive agents

Other studies have shown that the number of isotopically labelled microspheres localized in a region, following injection into the left heart, is a function of the relative blood flow to that region. The present studies show that the number of 10 size¹¹³Sn-labelled microspheres impacted in skin and various organs of rabbits under urethane anesthesia is directly proportional to the number of injected, over a wide range, with no evidence of saturation of the microcirculatory bed. At the lowest dose tested, there were 300 microspheres per skin site and at the highest dose an equalsized skin site contained 15,000 microspheres. Saline-injected test sites assayed 45 min after injection were not significantly different from uninjected sites. It was found that a standardized 177 mm² area of skin received 0.023±0.001% of the cardiac output. To assay various agents for their effect on dermal blood flow and to determine the time course of the effects, it was convenient to express the radio-activity of the test site as a ratio relative to the average radio-activity of uninjected skin sites. Standard errors less than 10% of the mean could be obtained when 13×10⁶ microspheres were injected into the left heart via a catheter in the carotid artery, providing 4 to 6 replicate test sites were averaged. It was possible to directly compare lesions from groups of animals. Enhanced blood flow was produced by the injection of histamine and bradykinin. The effect was transient and subsided by 20 min. Prostaglandin E₁ was the most potent mediator tested and its action lasted between 1–2 h. Casein, calcium pyrophosphate, carrageenan, endotoxin and glycoge were injected and their effect assayed at the arbitrary time of 100 min. Casein produced a 3-fold enhancement of blood flow. Calcium pyrophosphate gave a positive but mild (less than 2-fold) effect. The other agents had no effect. The intradermal injection of adrenalin significantly reduced the blood flow to normal skin, but this effect was confined to the site and did not affect adjacent test sites. The most pronounced blood flows were obtained following the injection of Freund's complete adjuvant and the flow to such sites was 6 to 9 times normal, from 1 to 14 days after injection. Triprolidine-HCl administered systemically significantly depressed the blood flow to normal skin, but this was overcome by the intradermal injection of casein, bradykinin and PGE. This assay has potential application to study the kinetics and the inhibition of this fundamental component of the inflammatory response.Supported by the Medical Research Council of Canada-MA 5056.     

Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs.

The effects of intravenous infusion of nitroglycerin (NTG), 8 and 32 microgram/kg.min for 7 min, and of sublingual NTG, 1.2 mg, were examined on direct and continuous measurements of systemic, coronary, and regional hemodynamics, left ventricular (LV) dimensions, pressures, and myocardial contractility in conscious dogs. NTG induced sustained reductions in LV dimensions and transient increases in heart rate and dP/dt, and decreases in mean arterial pressure. Initially NTG increased cardiac output and flows to the coronary, mesenteric, renal, and iliac beds, while systemic and regional vascular resistances fell. Later, cardiac output, cardiac work, and mesenteric and iliac flows fell significantly below control, and significant vasoconstriction in the systemic as well as mesenteric, iliac, and coronary beds was observed at a time when LV end-diastolic dimensions were still significantly reduced. Peripheral vasoconstriction was not observed with systemic NTG in deafferented dogs or when NTG, 1 microgram/kg.min, was infused intra-arterially into the iliac bed. Thus, systemic NTG induces a biphasic response consisting of initial arteriolar vasodilation followed by vasoconstriction in the mesenteric, iliac, coronary and systemic beds, which is presumably due to longer lasting effects on preload and to secondary reflex responses to the drug.     

Effect of nonachlazine and oxyfedrine on the coronary blood flow in dogs

The coronary blood flow in anesthetized and unanesthetized dogs was measured by means of an ultrasonic Doppler radiotelemetric apparatus. The ultrasonic transducer was placed on the upper third of the descending branch of the left coronary artery. Nonachlazine was shown to increase the coronary blood flow considerably in both anesthetized and unanesthetized dogs. However, the action of the substance lasted only 2–3 min and depended on changes in cardiac activity. Oxyfedrine increased the coronary bllod flow by a lesser degree than nonachlazine but for a longer time (mean 20 min). Considering the high effectiveness of the two substances in clinical practice the authors conclude that the increase in the coronary blood flow is not the main course of action when attempting to obtain an antianginal effect in patients with ischemic heart disease.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 1, pp. 34–38, January, 1977.