Decrease In Renal Vascular Resistance Research Articles

Influences of nifedipine on vascular conductance of portally drained viscera, liver and kidney

Nifedipine is a potent vasodilator, which induces various dose-related hemodynamic responses in the gastrointestinal tract, liver and kidney. Blood flow was assessed in anesthetized dogs with non-cannulating electromagnetic flow sensors. Nifedipine was injected into a brachial vein at intervals of 2 min in graded doses from 1–16 μg · kg −1. The pulsatile flow and pressure signals were analog-digital converted and processed by a computer program to obtain mean flow (ml · min −1) and mean pressure (mm Hg) values for every 3 s. The vascular data are presented as conductance. The arterial pressure decreased 45% while vascular conductance in vessels of the stomach, duodenum, small and large bowel increased between 75 and 128%. No response was observed in the splenic and common hepatic artery. An increase of resistance in the hepatic artery proper, while portal flow increased suggests that there were changes in liver metabolism. Although the literature indicates a decrease in renal vascular resistance, we encountered a decrease in flow but no change in resistance. Neither did we find an increase in heart rate. We propose that small intravenous doses of nifedipine reduce the afterload of the left ventricle.

Antihypertensive Drugs and Sodium Restriction: Analysis of Their Interaction Based on Pressure-Natriuresis Relationship

The hypotensive effects of some antihypertensive drugs are augmented under sodium restriction, while those of others are not. The mechanisms of these interactions were theoretically analyzed based on the arterial pressure-natriuresis relationship. Four-week studies were performed in 24 patients with essential hypertension who were given a regular sodium diet (12-15 g of NaCl/d) in the first and third weeks and a sodium-restricted diet (1-3 g/d) in the second and fourth weeks. One of three antihypertensive drugs, 60 mg/d of nicardipine (Ca-antagonist), 120 mg/d of propranolol (beta-blocker) or 150 mg/d of captopril (converting-enzyme inhibitor) was administered in the third and fourth weeks. The mean arterial pressure and urinary sodium excretion were measured on the last three days of each week. The degree of interaction between the antihypertensive drugs and sodium restriction was statistically compared. The hypotensive effect of nicardipine and propranolol did not differ with the change in sodium intake, whereas that of captopril was greater under sodium restriction than under the regular sodium diet. Urinary sodium excretion was plotted on the ordinate as a function of arterial pressure before and after administration of the antihypertensive drugs. The pressure-natriuresis curve was shifted left, without a change in the slope, by nicardipine and propranolol and also left, but with a decrease in the slope, by captopril. The hypotensive effect of nicardipine and propranolol, being independent of the amount of sodium intake, was based on the leftward shift of the pressure-natriuresis curve that was probably due to the decrease in renal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the prostaglandin E1 analog misoprostol on cyclosporine nephrotoxicity.

Acute infusion of cyclosporine in rats causes intense renal vasoconstriction and decreased glomerular filtration rate, effects that persist during short-term daily administration. We tested whether the orally active prostaglandin E1 analog misoprostol could reverse cyclosporine-induced renal vasoconstriction and restore the glomerular filtration rate. Male Sprague-Dawley rats were infused with cyclosporine (10 mg/kg) and then given an oral dose of misoprostol (100, 500, or 1000 micrograms/kg). Cyclosporine caused large decreases in glomerular filtration rate and renal blood flow and a large increase in renal vascular resistance. Misoprostol decreased renal vascular resistance and increased renal blood flow and glomerular filtration rate to near normal levels. The two highest doses of misoprostol caused severe hypotension only in cyclosporine-treated animals. However, when it was given in a dose of 100 micrograms/kg hypotension was not a serious problem. This dose of misoprostol resulted in an increase in glomerular filtration rate from 341 +/- 57 to 669 +/- 104 microliter/min (P less than 0.005) and renal blood flow from 2.23 +/- 0.36 to 4.25 +/- 0.65 ml/min (P less than 0.01), as well as a decrease in renal vascular resistance from 73.7 +/- 23.8 to 29.4 +/- 5.8 mmHg/ml/min (P less than 0.05) in cyclosporine-treated animals. When given to control animals, misoprostol had no effects on renal hemodynamics or renal function. In summary, acute cyclosporine-induced renal vasoconstriction and renal dysfunction in the rat were substantially reversed by oral administration of the prostaglandin E1 analog misoprostol.

Cardiovascular and renal effects of long-term antihypertensive treatment

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Cardiovascular and Renal Effects of Long-term Antihypertensive Treatment

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Effects of alpha 1 inhibition on renal blood flow and sympathetic nervous activity in systemic hypertension

Doxazosin is a competitive inhibitor of norepinephrine at α 1 adrenoceptors on vascular smooth muscle, where it blocks vasoconstriction. Twenty-four patients with mild hypertension were treated with either doxazosin or placebo for 6 weeks. Supine and upright mean arterial pressures decreased by 9 and 12 mm Hg, respectively, in patients receiving doxazosin. This decrease was significantly more than the blood pressure change with placebo (p < 0.05). Doxazosin therapy led to a small increase in weight (p < 0.05). It was also associated with a statistically insignificant decrease in renal vascular resistance (568 dynes s/cm 5) so that renal blood flow and creatinine clearance did not change. Doxazosin increased renin levels acutely and norepinephrine levels with 6-week treatment, but these changes were not significantly different from placebo. Norepinephrine clearance, measured after a 120-minute infusion of 3H norepinephrine, did not change. Heart rate increased acutely after doxazosin administration, but returned to baseline during 6-week therapy. Blood pressure, measured hourly for 14 hours after treatment, was consistently decreased in all patients. Doxazosin taken once daily lowers blood pressure without affecting renal blood flow or heart rate.

Ontogeny of renal hemodynamic response to renal nerve stimulation in sheep.

The renal hemodynamic response to direct electrical stimulation of renal nerves was studied in conscious and chronically instrumented fetal (130-142 days gestation; term 145 days), newborn (7-12 days postnatal), and adult nonpregnant sheep. Renal nerve stimulation (RNS) produced a significant decrease in renal blood flow (RBF) velocity and a significant increase in renal vascular resistance (RVR) in all three groups of animals. The overall decline in RBF velocity and the overall rise in RVR was less pronounced in fetal than in adult sheep (P less than 0.05). Changes in RBF velocity and RVR using an RNS frequency of 16 Hz were -35 +/- 4 and 81 +/- 19% in fetal sheep, -61 +/- 10 and 374 +/- 128% in newborn lambs, and -84 +/- 12 and 540 +/- 94% in adult sheep, respectively. RNS during intrarenal infusion of the alpha-adrenoceptor antagonist phentolamine was associated with a significant increase in RBF velocity and decrease in RVR in both fetal sheep and newborn lambs, but not in adult sheep. Moreover, it was found that the rise in RBF velocity and the decrease in RVR associated with RNS during alpha-adrenoceptor antagonism were completely inhibited by intrarenal infusion of ICI 118,551, a beta 2-adrenoceptor antagonist and unaffected by either cholinergic or dopaminergic antagonists. Taken together, these results suggest that the overall renal vasoconstrictor response to RNS is age dependent. Furthermore, the present results demonstrate that, contrary to observations made in adult animals, RNS can produce renal vasodilation in immature animals that is mediated by beta 2-adrenoceptors.

Osmotic Diuresis

Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs.

Acute renal effects of oral felodipine in normal man.

The acute renal effects of a single oral dose of felodipine 0.15 mg/kg were studied in 8 healthy males. Thirty minutes after administration the mean plasma concentration was 25.7 nmol/l. There was a significant reduction in diastolic blood pressure (24%) and a concomitant rise in heart rate (38%), leaving the systolic pressure unchanged. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique using the clearance of 125I-iothalamate and 131I-hippuran respectively. GFR was unchanged and the filtration fraction (FF) was reduced, whilst there was a decrease in renal vascular resistance (RVR). The glomerular filter characteristics were unchanged, as estimated by the unchanged excretion rate of albumin. There was a significant rise in the clearance of sodium (176%) but only a small and insignificant increase in urine volume. Clearance of potassium was decreased. An increase in the clearance of uric acid and a rise in the beta-2-microglobulin excretion rate were found, both suggesting a proximal tubular effect of felodipine. The excretion rate of calcium was increased.

Renal vasodilatation after inhibition of renin or converting enzyme in marmoset.

The relative importance of angiotensin II for the renal vasodilatory response after converting-enzyme inhibition was evaluated by a comparison of the effects of converting-enzyme and renin inhibition on renal vascular resistance. Renal, mesenteric, and hindquarter blood flows were measured with chronically implanted ultrasonic-pulsed Doppler flow probes in conscious, mildly volume-depleted marmosets after administration of a converting-enzyme inhibitor (enalaprilat, 2 mg/kg iv), a synthetic renin inhibitor (CGP 29,287, 1 mg/kg iv), or a renin-inhibitory monoclonal antibody (R-3-36-16, 0.1 mg/kg iv). Enalaprilat reduced blood pressure (-16 +/- 4 mmHg, n = 6) and induced a selective increase in renal blood flow (27 +/- 8%, n = 6). CGP 29,287 and R-3-36-16 induced comparable reductions in blood pressure (-16 +/- 4 mmHg, n = 6 and -20 +/- 4 mmHg, n = 5, respectively) and selective increases in renal blood flow (36 +/- 12%, n = 6 and 34 +/- 16%, n = 4, respectively). The decrease in renal vascular resistance was of similar magnitude for all of the inhibitors (enalaprilat -28 +/- 3%, CGP 29,287 -32 +/- 6%; and R-3-36-16 -33 +/- 7%). These results indicate that the renal vasodilatation induced after converting-enzyme or renin inhibition is mainly due to decreased formation of angiotensin II.

The contribution of PGI2 to the effects of captopril in conscious dogs in differing states of sodium balance

There is some evidence that increased prostaglandin synthesis may mediate some of the effects of the angiotensin converting enzyme inhibitor captopril. The potential role of prostaglandin (PG)I2 in this process was assessed by measurement of changes in urinary 6-keto-PGF1 alpha excretion after captopril in eight sodium replete and depleted conscious dogs. In sodium replete animals captopril induced a small decrease in blood pressure, transient increases in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, and progressive increases in plasma renin activity (PRA) and urinary sodium excretion. By contrast, during sodium depletion captopril induced a large decrease in blood pressure, a transient increase in effective renal plasma flow and urinary 6-keto-PGF1 alpha excretion, an early large but transient increase in PRA and small progressive increase in sodium excretion. The time course of changes after captopril suggested that increased PGI2 synthesis may contribute to the transient decrease in renal vascular resistance. The increase in PRA during sodium depletion was not associated with any change in urinary 6-keto-PGF1 alpha excretion.

Effects of calcium channel blockade on renal vascular resistance responses to changes in perfusion pressure and angiotensin-converting enzyme inhibition in dogs.

We conducted these experiments to evaluate the selectivity of calcium channel blockade on the renal autoregulatory mechanism and on angiotensin II-mediated renal vasoconstriction. Experiments were performed in anesthetized dogs in which renal arterial pressure, renal blood flow, and glomerular filtration rate were measured at normal and reduced renal arterial pressure. At control arterial pressures, renal arterial infusions of verapamil increased renal blood flow and glomerular filtration rate significantly. The decreases in renal vascular resistance elicited with verapamil (n = 13) and nifedipine (n = 4) occurred only at renal arterial pressure levels within the normal autoregulatory range. Renal blood flow autoregulatory efficiency was markedly attenuated, and the pressure-flow relationship obtained during calcium channel blockade approached that of a passive system. Systemic infusions of an angiotensin-converting enzyme inhibitor (captopril) during continued verapamil infusion caused further vasodilation at all renal arterial pressure values, as evidenced by an increase in slope of 27% of the pressure-blood flow relationship. This response was reversed by angiotensin II infusions. This shift indicates a reduction in minimal vascular resistance elicited by captopril, not obtainable with verapamil alone, and sensitive to angiotensin II. The effects of verapamil and nifedipine on renal blood flow autoregulation suggest a specific effect at preglomerular sites of potential operated membrane calcium channels in the autoregulatory phenomenon. The additional vasodilation elicited with captopril and reversed by angiotensin II indicates the presence of an angiotensin-sensitive postglomerular resistance component which is not influenced by calcium entry blockers.

Effect on renal haemodynamics, glomerular filtration rate and albumin excretion of high oral protein load.

The effect on glomerular filtration rate (GFR), renal plasma flow (RPF) and excretion of albumin and beta-2-microglobulin in the urine after a high oral protein or amino acid load was investigated in young healthy males. After both test meals an increase in GFR of 10%, and in RPF of about 9-18%, was seen. The filtration fraction and albumin excretion rates were unchanged. The increase in GFR was significant from 20 to 60 min after intake of meat and remained elevated for more than 2 h. After the meat meal, a decrease in renal vascular resistance and an increase in S-creatinine, S-phosphate, S-carbamide and beta-2-microglobulin excretion rates was seen, but not after the amino acid load. During the experiments a gradual decrease in S-protein was noted. We conclude that the increase in RPF and GFR caused by intake of protein or amino acids in short-term experiments is not associated with impaired permselective properties of the glomerular membrane expressed in the albumin excretion rate.

Formation of biogenic amines by isolated kidneys of spontaneously hypertensive rats

Kidneys form dopamine (DA) from L-dopa and serotonin from L-5-hydroxytryptophan (L-5-HTP) via aromatic L-amino acid decarboxylase. We compared the ability of isolated perfused kidneys from adult (20-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to form these biogenic amines. Renal vascular resistance (RVR) was greater in perfused kidneys from SHR (n = 10) than WKY (n = 8) (p < 0.01). Slight decreases in RVR were observed during L-dopa infusion but these were unrelated to DA formation. L-Dopa infusion was associated with greater DA output in SHR than WKY in both the renal venous and urinary effluents although the latter did not achieve statistical significance. L-5-HTP increased RVR to a greater degree in SHR than WKY kidneys. This was associated with larger quantities of serotonin in the urinary and venous effluents and greater pressor responses to exogenous serotonin in SHR than WKY kidneys; however, either parameter alone was not significantly increased. Our findings do not support a deficiency of intrarenal DA formation as a pathogenic factor for hypertension in SHR. Biogenic amine formation is as great if not greater in SHR than WKY kidneys and appears to contribute largely to the greater increases in renal resistance seen in SHR kidneys on infusion of L-5-HTP. Enhanced renal serotonin formation may elevate blood pressure, whereas enhanced renal DA formation would favor blood pressure lowering, perhaps as a compensatory mechanism.

Long-term renal and systemic effects of calcium entry blockers in normotensive and experimental hypertensive dogs

The effect of diltiazem administered as a sustained infusion (10 to 15 μg/kg/min) was studied in 3 groups of conscious instrumented dogs: 4 normotensive, 5 Goldblatt hypertensive (GH) and 4 deoxycorticosterone acetate-salt treated Goldblatt hypertensive (DSGH) dogs. Mean arterial blood pressure, left renal blood flow and heart rate were monitored, and the plasma renin activity was determined in a control session and after 3 to 5 days of diltiazem infusion in the normotensive and after 5 to 8 days of infusion in the 2 hypertensive groups. Pressor and renal blood flow responses to phenylephrine, norepinephrine and angiotensin II were also determined in the control session and on the last day of the diltiazem infusion. Mean arterial blood pressure was found to be decreased at the 5 to 8-day interval in the DSGHs and in the GHs, but the change in the latter group was not statistically significant. Mean arterial blood pressure was unchanged in the normotensives. Renal vascular resistance was decreased by diltiazem in the normotensive group at 3 to 5 days and in the DSGHs at 1 to 2 days. Heart rate was not significantly affected by diltiazem in the hypertensive groups, but was increased in the normotensive group at the 1 to 2-day interval. Plasma renin activity tended to increase in the hypertensive, but not in the normotensive dogs. Pressor and renal blood flow responses to all the agonist agents tested were decreased in the presence of diltiazem. The hypotensive effect of diltiazem was more prominent in the conscious DSGHs than in the normotensive dogs or GHs; a decrease in renal vascular resistance was seen in both the normotensive and DSGH groups. Hypotension in these animals may be related at least in part to depression of vasoconstrictor stimuli.

Effect of halothane on renal hemodynamics during normovolemia and acute hemorrhagic hypovolemia.

The effects of halothane on renal hemodynamics under both normovolemic and hypovolemic conditions were investigated in chronically instrumented conscious dogs whose homeostatic mechanisms were not altered by the presence of preexisting drugs. Renal blood flow and aortic pressure were assessed by prior implantation of Doppler ultrasonic flow probes on the renal artery and a catheter in the descending aorta. Administration of halothane to conscious normovolemic dogs (Group HN) resulted in 11-26% decreases in renal vascular resistance with no significant changes occurring in renal blood flow. In a second group of animals made hypovolemic while awake (Group AH), 30% of the blood volume was removed over one-half hour. In response to hemorrhage, these conscious animals' renal blood flow did not significantly change from the normovolemic control, and renal vascular resistance significantly decreased. With no further intervention, renal vascular resistance and renal blood flow remained unchanged from the level achieved after the 30% hemorrhage. A third group of animals (Group HH) was hemorrhaged in a manner similar to that of Group AH. They also showed no significant changes in renal blood flow and a significant decrease in renal vascular resistance in response to hemorrhage. Thereafter, administration of halothane, as in Group HN, to this group produced 11-23% decreases in renal vascular resistance with no significant decline in renal blood flow from the hypovolemic control levels established after hemorrhage. The author concludes the following: administration of halothane to normovolemic conscious dogs does not decrease renal blood flow; a moderate degree of acute hemorrhagic hypovolemia does not decrease renal blood flow in conscious dogs; and administration of halothane to acutely hypovolemic conscious dogs does not impair renal perfusion.

The effects of human atrial 28-amino acid peptide on systemic and renal hemodynamics in anesthetized rats.

The effects of synthetic human atrial 28-amino acid peptide (alpha-human atrial polypeptide) on systemic and renal hemodynamics were examined in two separate groups of Inactin-anesthetized rats. First, mean arterial pressure, heart rate, and cardiac output were measured before and during infusion of the peptide at rates of 0.04-0.67 microgram/kg per min. Cardiac output was determined by the dye-dilution method with a microcuvette inserted into a carotid-femoral arterial shunt. After 10 minutes of infusion, mean arterial pressure, cardiac output, and total peripheral resistance were reduced in a dose-dependent manner by 21% (P less than 0.001), 9% (P less than 0.05), and 11% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. Despite the marked fall in blood pressure, the heart rate did not change. Second, urine volume, urinary sodium excretion, glomerular filtration rate ([3H]inulin clearance) and renal blood flow ([14C]p-aminohippuric acid sodium clearance and hematocrit) were measured. Increases in urine volume, urinary sodium excretion, filtration fraction, and fractional sodium excretion and a decrease in renal vascular resistance were dose dependent: +490% (P less than 0.01), +1340% (P less than 0.01), +19% (P less than 0.05), +1160% (P less than 0.01), and -18% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. The glomerular filtration rate increased with 0.33 and 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide (both P less than 0.05), whereas renal blood flow did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and Renal Hemodynamic Responses to Vascular Blockade of Vasopressin in Conscious Dogs with Ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.

1625 RENAL NEUROADRENERGIC TRANSMISSION DURING FETAL LIFE

The renal vasoconstrictor response to graded (0.2 to 3.0 Hz, 20V, 1 msec) direct electrical renal nerve stimulation (RNS) was studied in 9 chronically catheterized fetal (F) lambs (130-142 days gestation; term 145 days) and 3 adult (A) sheep. Changes in renal blood flow (RBF) were monitored using a doppler flow-meter. During RNS, RBF (r=-0.98) decreased and renal vascular resistance (RVR) (r=0.98) increased in a dose-response relation in F and A. Following administration of phentolamine, a rise in RBF (+57% at 1.0 Hz) and a decrease in RVR (-32% at 1 Hz) were observed in F; these changes were not completely blocked with propranolol. At low frequency ( 0.4 Hz) of RNS, % changes in RBF and RVR were significantly higher in F than in A. (*for p<0.05 when F compared to A) In summary these results demonstrate that during fetal life 1) renal hemodynamics seems to be more sensitive to low frequency RNS than in A; 2) renal vasoconstriction following RNS is dependent on α adrenoceptors; and 3) renal vasodilation produced by RNS during α-blockade is not fully dependent on activation of β-adrenoceptors.

The role of histamine H1 and H2 receptors in the canine kidney.

The functional role of H1 and H2 receptors in mediating the effects of histamine on renal hemodynamics and tubular function was investigated in anesthetized dogs. Histamine, infused directly into the renal artery, caused decreases in renal vascular resistance and increases in total renal blood flow without significant changes in mean arterial blood pressure or glomerular filtration rate. These hemodynamic effects of histamine were inhibited by the H2-receptor antagonist, cimetidine, but not by the H1-receptor antagonist, tripelennamine. Histamine also caused increases in fractional urine flow and the fractional excretion of sodium and calcium with a concomitant decrease in urine/plasma osmolality. These tubular effects of histamine were antagonized by both tripelennamine and cimetidine. Histamine-induced increases in the fractional excretion of potassium were blocked only by tripelennamine. These results suggest that (1) both H1 and H2 receptors mediate the effects of histamine on urinary dilution and tubular reabsorption; (2) H2 receptors mediate the effects of histamine on renal hemodynamics, indicating that H2 receptors are present in the renal vasculature, and (3) H1 receptors may exist in the renal tubules.