An up-regulation of renal alpha(2)A-adrenoceptors is associated with resistance to salt-induced hypertension in Sabra rats.

This study investigates the incidence of high-salt diet in blood pressures, renal alpha(2)-adrenoceptor subtypes distribution, and gene expression in salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats. Comparisons have been made between SBH and SBN rats submitted to a normal or a high-salt diet for 6 weeks. Only alpha(2)B-adrenoceptors are detected in kidneys of SBH rats, whatever the diet. In contrast, mRNA corresponding to alpha(2)A- and alpha(2)B-subtypes are found in this substrain. In these rats, high-salt diet increases blood pressures and up-regulates gene expression and density of only alpha(2)B-adrenoceptors. Inversely, alpha(2)A- and alpha(2)B-adrenoceptors and corresponding mRNA are found in kidneys of SBN rats. In these rats, a high-salt diet does not affect blood pressures but increases gene expression and densities of both alpha(2)A- and alpha(2)B-adrenoceptors. If the up-regulation of renal alpha(2)B-adrenoceptor subtypes is indicative of the hypertensive phenotype, the present study shows that this mechanism is also present in normotensive salt-resistant Sabra rats. In fact, the absence of alpha(2)A-adrenoceptors in SBH could be responsible for the lack of adequate receptor-mediated renal functions predisposing to salt-sensitivity and consequently the development of hypertension. Conversely, the presence of this receptor in SBN rats and its up-regulation could be protective change against the increase of alpha(2)B-adrenoceptors induced by the salt overload and could consequently be responsible for the resistance to salt-induced hypertension.

Hypertension in cafeteria-fed rats: alterations in renal alpha2-adrenoceptor subtypes.

Obesity is a major cause of human essential hypertension and there are clear evidences that abnormal kidney functions play a key role in obesity hypertension. Feeding rats a cafeteria diet has been extensively used as an experimental model to study obesity and energy balance expenditure. The present study investigated whether rats fed a cafeteria diet develop hypertension with alterations in renal alpha2-adrenoceptor subtype distribution. Weight gain induced by feeding rats a cafeteria diet during 8 weeks was associated with a marked increase in blood pressure. Insulin levels were higher in these hypertensive rats, leading to a decreased plasma glucose/insulin ratio. Based on radioligand-binding studies using [3H]-RX821002 and selective competitors, a raise in alpha2-adrenoceptor density that was solely due to an increased alpha2B-adrenoceptor subtype density was detected in the kidney of the cafeteria-fed rat. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) experiments showed an overexpression of the gene encoding the alpha2B-adrenoceptor subtype in these rats. On the other hand, despite a similar mRNA level, the alpha2A-adrenoceptor subtype was no more detectable by radioligand-binding studies in the kidney of the cafeteria-fed rat. In conclusion, cafeteria-fed rats are hypertensive, with renal alterations in alpha2-adrenoceptor distribution. These alterations, which are not related to genetic factors, may play a key role in the onset of hypertension.

Patterns of messenger RNA expression for alpha1-adrenoceptor subtypes in human corpus cavernosum.

PURPOSE: The present study evaluated the expression of alpha1-adrenoceptor subtypes in human corpus cavernosum. MATERIALS AND METHODS: The mRNA encoding alpha1a, alpha1b and alpha1d subtypes were assessed by RNA-directed complementary cDNA synthesis followed by Taq DNA amplification. The level of alpha1 mRNA was calculated in arbitrary optical density units and normalized with respect to the length of the respective cDNA fragments. RESULTS: We found that alpha1a, alpha1b and alpha1d adrenoceptor subtypes are expressed in human corpus cavernosum, with a predominant expression of the alpha1a subtype. CONCLUSION: These results suggest that alpha1a-adrenoceptor subtype is important and that understanding the biochemical and functional characteristics of this subtype may lead to the development of specific antagonists in the treatment of impotence.

Insulinemia and pancreatic alpha2-adrenoceptors in salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats: effect of high salt diet.

Studies in humans have suggested that hyperinsulinemia might play an important role in salt sensitivity and in the later development of high blood pressure. This possibility has been tested in this study on Sabra rats, an animal model of salt-induced hypertension. Salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats have been submitted to either a normal (0.2% NaCl) or a high salt (8% NaCl) diet for 6 weeks. Comparisons of blood pressure, basal glucose and insulin levels, and insulin response to glucose overload (1 g/kg) have been made. As pancreatic alpha2-adrenergic receptors are implicated in the control of insulin release, their densities have been determined on plasma membranes by saturation studies with [3H]-RX-821002 as the specific radioligand. Under normal diet, blood pressures were respectively 133 +/- 9 and 108 +/- 10 mm Hg (n = 6) in SBH and SBN. Basal glucose and insulin levels and insulin response to glucose overload were found to be significantly higher in SBH than in SBN. In contrast, alpha2-adrenergic receptor densities were lower (P < .001) in SBH when compared to SBN. High salt diet increased (P < .01) blood pressure, decreased basal glucose (P < .01) and insulin (P < .001) levels only in SBH. However, when compared to SBN the insulin response to glucose overload was maintained higher in SBH. Alpha2-adrenergic receptor densities and difference between SBH and SBN did not differ from those found in normal diet. In conclusion, the salt-induced high blood pressure of salt-sensitive Sabra rats is not associated with hyperinsulinemia and insulin resistance. Indeed, an improvement in the insulin sensitivity appears to be induced by either a high salt diet or high blood pressure.

[Evidence for two alpha 2B-adrenoreceptor isoforms in the renal cortex of salt-sensitive and salt resistant Sabra rats. Effect of salt loading]. / Distinction de deux isofromes de récepteurs alpha 2B-adrénergiques dans le cortex rénal des rats Sabra sensibles et résistants au sel. Effet d'une surcharge en sel.

alpha 2-adrenoceptors are involved in various renal functions regulating blood pressure. They were classified in subtypes whom genes were identified in both humans and rats. In rat renal cortex it was evidenced that the alpha 2B isoform is predominant. This result was confirmed in Sabra rats. However, the renal cortex alpha 2B density is higher in salt-sensitive (SBH) than in salt-resistant (SBN) Sabra rats. alpha 2B-adrenoceptors were recently subclassified in two pharmacologically distinct subtypes exhibiting high and low affinity for guanoxabenz and respectively called alpha 2B1 and alpha 2B2. We studied sodium loading effect on alpha 2B1 and alpha 2B2 distribution in Sabra rat renal cortex using competition experiments between [3H]-yohimbine and guanoxabenz. The rats were submitted to normal (0.2%) or high sodium diet (8%) for six weeks. Under normal diet, proportion alpha 2B1 and alpha 2B2 was similar in SBH and SBN. Nevertheless, their respective densities were significantly higher in SBH as compared to SBN (alpha 2B1: 90.6 +/- 4.1 vs 57.4 +/- 2.5 fmoles/mg prot, p < 0.0001; n = 5; alpha 2B2: 102.7 +/- 4.0 vs 66.4 +/- 4.6 fmoles/mg prot; p < 0.0001; n = 5). Under high sodium diet the distribution of these two isoforms was altered. The densities of alpha 2B1 were decreased by 27.0 +/- 5.9% in SBH (68.0 +/- 4.0 fmoles/mg prot; p < 0.0001, n = 5) and by 47.3 +/- 7.4% for SBN (29.2 +/- 3.1 fmoles/mg prot; p < 0.0001; n = 5). Conversely, the densities of alpha 2B2 were increased by 28.3 +/- 5.4% in SBH (131.1 +/- 9.5 fmoles/mg prot; p < 0.001; n = 5) and by 75.0 +/- 17% in SBN (123.2 +/- 9.1 fmoles/mg prot; p < 0.0001; n = 5). In conclusion, alpha 2B1- and alpha 2B2-adrenoceptor subtypes are found in renal cortex of both SBH and SBN. Our data demonstrated an equal distribution of these two isoforms between SBH and SBN under normal salt diet. This distribution is largely altered, especially in SBN, by the high sodium diet. From these modifications might result differential renal responses to activation of alpha 2B-adrenoceptors between SBH and SBN, and consequently responsible for normal or high blood pressure after high sodium diet.

Differential distribution of alpha 2-adrenoceptor subtypes and messenger RNA expression between renal cortex of salt-sensitive and salt-resistant Sabra rats.

OBJECTIVE: To assess whether alterations of alpha 2-adrenoceptor subtypes in distribution and gene expression in the renal cortex could explain the predisposition to salt-sensitivity or salt-resistance in Sabra rats. DESIGN: Studies were performed using plasma membranes and RNA preparations from renal cortex of 8- to 10-week-old Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats on a normal-sodium diet. METHODS: The alpha 2-adrenoceptor subtypes were determined by competition experiments with [3H]-yohimbine or [3H]-RX821002. Their gene expression was studied by RNA-directed complementary DNA synthesis followed by Taq DNA polymerase amplification. RESULTS: Binding studies showed that alpha 2B- and alpha 2A-adrenoceptor subtypes represented in SBN 72 and 28% of the maximal binding capacities of the two radioligands, respectively. In contrast, only the alpha 2B subtype was detected in the SBH rat. However, the use of guanoxabenz disclosed alpha 2B-adrenoceptors in alpha 2B1 and alpha 2B2 subtypes. The densities of those alpha 2B subtypes appeared to be higher in the SBH rat than in the SBN rat. Messenger RNA corresponding to alpha 2A and alpha 2B subtypes were found both in SBH rats and in SBN rats. The expression of the alpha 2B subtype was permanently higher in the SBH rats than in the SBN rats. The expression of the alpha 2A gene in the SBH rats suggests a specific SBH post-transcriptional regulation resulting in the absence of alpha 2A-adrenoceptor. CONCLUSIONS: Differences exist in the renal cortex concerning expression and distribution of alpha 2-adrenoceptor subtypes between SBH and SBN rats. From these differences there might result different alpha 2-adrenoceptor-mediated renal functions in SBH and in SBN rats, which could lead to a predisposition to sensitivity or resistance to a high sodium intake.

Differential sodium regulation between salt-sensitive and salt-resistant Sabra rats is not due to any mutation in the renal alpha 2B-adrenoceptor gene.

A defect in sodium modulation of density and agonist affinity of renal alpha 2-adrenoceptor exists in normotensive salt-resistant Sabra (SBN) rats when compared to hypertensive salt-sensitive (SBH). A highly conserved aspartic acid residue in the second helix has been implicated in sodium regulation of alpha 2-adrenoceptor-ligand interactions. As the alpha 2B-adrenoceptor subtype is preponderantly present in kidney of SBH and SBN rats, a mutation might distinguish this subtype between SBH and SBN rats. From this study, no difference between SBH and SBN alpha 2B-adrenoceptor gene could be demonstrated in terms of nucleotide sequence. These data suggest that in Sabra rats, the differential sodium regulation in density and agonist affinity between renal SBH and SBN alpha 2-adrenoceptor may have another origin than the alpha 2B-adrenoceptor encoding gene.

Enhancement of the expression of the alpha 2-adrenoreceptor protein and mRNA by a direct effect of androgens in white adipocytes.

In vivo, testosterone-treatment of female hamsters for 4 days promotes a doubling of alpha 2-adrenoreceptor protein in parametrial adipocytes, with a concomitant accumulation of the alpha 2A-adrenoreceptor subtype mRNA. During in vitro incubation of minced parametrial fat pads for 6 to 48h with testosterone or dihydrotestosterone (100 nM), alpha 2A-adrenoreceptor protein and mRNA levels were also increased and remained to control levels when an antiandrogen or actinomycin D were added in the medium. It is concluded that in hamster adipocytes, androgens upregulate alpha 2A-adrenoreceptor subtype expression at the mRNA level by an androgen receptor-dependent transcriptional activation.

Influence of ovarian status and regional fat distribution on protein kinase C in rat fat cells.

The effects of ovarian status on insulin- and phorbol 12-myristate 13-acetate (TPA)-stimulated lipogenic responses, phorbol ester-specific binding to protein kinase C (PKC) and immunoblot-quantified beta- and epsilon-PKC isoform levels were compared in female rat fat cells from subcutaneous and deep intra-abdominal (parametrial) fat deposits. In control rats, the cytosolic PKC content per cell was 70% lower in subcutaneous than in parametrial adipocytes. In subcutaneous and parametrial fat cells, the cytosolic PKC contents were reduced by ovariectomy and restored to normal by the administration of ovarian hormones (oestradiol plus progesterone). However, the lipogenic response to TPA was unaltered by ovarian status in both fat deposits, contrasting with the insulin-stimulated lipogenic response. This response increased in parametrial fat cells after ovariectomy and returned to normal after ovarian hormone treatment whereas, in subcutaneous fat cells, the insulin response was either unaltered by ovariectomy or increased by the administration of ovarian hormones. This study shows important site-related differences in fat cell PKC content but also reveals a similar modulation of this PKC by ovarian status, regardless of the anatomical localization of the fat cells. The physiological significance of these findings is discussed.

Regulation of white adipocyte guanine nucleotide binding proteins Gs alpha and Gi alpha 1-2 by testosterone in vivo: influence of regional fat distribution.

The influence of the androgenic status on the steady-state amounts of Gi alpha 1-2 and Gs alpha subunits was compared in hamster fat cell membranes from the femoral subcutaneous (FSC) and epididymal (EP) adipose tissues, using immunoblotting experiments. In sham-operated hamsters, Gi alpha 1-2 and Gs alpha steady-state amounts found in FSC fat cells were 38% and 40% reduced, respectively, as compared to EP adipocytes. In EP fat cells, castration induced a down-regulation of both Gi alpha 1-2 (-39%) and Gs alpha (-33%), whereas testosterone replacement restored Gs alpha, but not Gi alpha 1-2 levels, to control values. In contrast, these G protein alpha-subunits were insensitive to the androgenic status in FSC fat cells. These data provide the first evidence that the androgenic status can modulate the expression of both the Gi alpha 1-2 and Gs alpha subunits of the fat cell adenylate cyclase regulatory Gi and Gs proteins and that this modulation depends on the anatomical origin of these cells.

[Na+/H+ exchangers, alpha-2-adrenergic receptors, sodium sensitivity and arterial hypertension]. / Echangeurs Na+/H+, récepteurs alpha 2-adrénergiques, sensibilité au sodium et hypertension artérielle.

Existing evidences indicate that a crossed regulation between alpha 2-adrenergic receptors and Na+/H+ exchanger(s) exists, that Na decreases the affinity of alpha 2-adrenergic receptors for agonists and antagonists, that intracellular Na+ and H+ ion concentrations regulate Na+/H+ exchanger activity, that intracellular pH controls the affinity of the alpha 2-adrenergic receptors for their agonists and antagonists. Alterations of alpha 2-adrenergic receptor densities and allosteric regulation by sodium have been demonstrated in sodium-dependent hypertension in rats. Increased Na+/H+ exchanger activity has been reported in genetic hypertension. Nevertheless, cosegregation experiments and human genetic polymorphism suggest that the exchanger could not be related to hypertension. We propose the following hypothesis: the increased Na+/H+ exchanger characteristic of hypertension could be secondary to the abnormalities of the alpha 2-adrenergic receptors found in hypertension, probably through the alteration of the sodium allosteric effect on these receptors.

Non-adrenergic binding sites for the "alpha 2-antagonist" [3H]idazoxan in the rabbit urethral smooth muscle. Pharmacological and biochemical characterization.

In the present study, pharmacological and biochemical binding characteristics of [3H]idazoxan, an originally thought alpha 2-adrenoceptor antagonist, have been determined in smooth muscle of rabbit urethra. It is shown that [3H]idazoxan labels with high affinity non-adrenergic binding sites. Specific binding of [3H]idazoxan is inhibited by compounds possessing an imidazoline or a guanidinium moiety whereas phenylethanolamines and classical alpha 2-antagonists are ineffective competitors which suggests an imidazoline-preferring binding site. However, imidazolidines such as clonidine and paminoclonidine are poorly effective, which differs considerably from pharmacological characteristics of imidazoline binding sites previously reported in the central nervous system. In addition, it is shown that K+ and Mn2+ inhibit [3H]idazoxan binding in a competitive and non-competitive manner, respectively. Other cations such as Na+, Li+ and Mg2+ have no significant effect. It is shown that K+ accelerates the dissociation of [3H]idazoxan binding while Mn2+ does not produce any modification. These results suggest that K+ may bind to an allosteric site, while Mn2+ may bind with a membrane component susceptible to alter [3H]idazoxan binding sites.

Sodium regulation in the affinity of renal alpha 2-adrenoceptors for epinephrine in Sabra salt-sensitive and salt-resistant rats.

Sodium ions markedly decreased in vitro renal alpha 2-adrenoceptor affinity for epinephrine in Sabra hypertensive (SBH) but not in normotensive (SBN) rats. Under these conditions, affinity of alpha 1-adrenoceptor for epinephrine was unchanged in SBH and SBN rats. If these data could be confirmed in vivo, the sodium ion, by acting as an inhibitor, could modify the effect of agonists on renal alpha 2-adrenoceptors in SBH rats. Conversely, the absence of sodium regulation in SBN rats might represent a genetically mediated change responsible for the resistance to the development of salt-induced hypertension.

Non-adrenergic binding sites for the "alpha 2-antagonist" [3H] idazoxan in rabbit urethral smooth muscle.

In the present study, we have provided evidence that [3H] rauwolscine and [3H] idazoxan bind to different sites in rabbit urethra. The [3H] idazoxan capacity and affinity was 215 +/- 14 fmol/mg protein and 1.59 +/- 0.16 nM while [3H] rauwolscine binding parameters were 45.9 +/- 3.4 fmol/mg protein and 2.39 +/- 0.27 nM. [3H] idazoxan specific binding was inhibited only by compounds possessing an imidazoli(di)ne or a guanidinium moiety, while [3H] rauwolscine specific binding was inhibited by phenylethanolamines and classical alpha 2-antagonists. [3H] idazoxan was inhibited by KCl in a competitive and by MnCl2 in a non-competitive way, while other cations such as Na+, Li+ and Mg2+ did not inhibit [3H] idazoxan binding. Moreover, we investigated the regional distribution of [3H] idazoxan and [3H] rauwolscine along the rabbit urethra using quantitative autoradiography. Analysis of the films revealed a different distribution of these two binding sites on the urethral sections.

[Binding sites of imidazolines. Study with (3H)-idazoxan in renal cortex of Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats]. / Sites de liaison des imidazolines. Etude avec l'(3H)-idazoxan dans le cortex rénal des rats Sabra sensibles (SBH) et résistants (SBN) au sel.

Imidazoline binding sites have been characterized in organs modulating blood pressure, such as brain and kidney with (3H)-p-aminoclonidine and (3H)-Idazoxan respectively. However, the pharmacological characteristics of the imidazoline-preferring binding sites differ considerably depending on the species investigated and the radioligand used. Little is known about the physiological relevance of the non-adrenergic (3H)-idazoxan binding sites. As some imidazolines and certain alpha-adrenoceptor agonists possess antihypertensive activity, an alteration of these binding sites should be considered as a possible causes in the development of hypertension. In the present study, we performed binding studies with the imidazoline ligand (3H)-idazoxan in renal cortex of hypertensive salt-sensitive (SBH) and normotensive salt-resistant (SBN) Sabra rats. (3H)-idazoxan binding capacities were higher in SBH than in SBN rats. Competition studies have shown for (3H)-idazoxan specific binding non-adrenergic characteristics exclusively. In these both substrains, (3H)-idazoxan binding exhibit pharmacological profile of imidazoline binding sites. However, theses sites have also high affinity for guanidino compounds and amiloride. Surprisingly, amiloride and some analogues were significantly more potent in SBN than in SBH rats. From this study, it is difficult to elucidate the physiological role of imidazoline binding sites in renal cortex. However, differences observed between SBN and SBH suggest that these sites may play a role in the development of hypertension in Sabra rats.

Amiloride interacts with [3H]idazoxan and [3H]rauwolscine binding sites in rabbit urethra.

Amiloride and its analogues (N-ethylisopropylamiloride and banzamil) interact more potently with [3H]idazoxan binding sites (nM range) than with [3H]rauwolscine binding sites (microM range) in the rabbit urethra. The binding of both radioligands was competitivelly inhibited by amiloride, with increased KD values and no change in their binding capacity. Interestingly, amiloride was a potent inhibitor at [3H]idazoxan binding sites in rabbit urethral smooth muscle at concentrations far below those required to inhibit the Na+/H+ exchanger or electrogenic pump.

Alpha-adrenoceptor properties in rat strains sensitive or resistant to salt-induced hypertension.

Cerebral and renal alpha 2-adrenoceptors are implicated in the control of sympathetic activity and of sodium reabsorption respectively. In addition, sodium ions play an important role in the regulation of either alpha 2-adrenoceptor densities and affinities for adrenergic agonists. In the present study, alpha-adrenoceptor properties were investigated in genetically predetermined salt-sensitive and salt-resistant Dahl and Sabra rats. Cerebral alpha 2-adrenoceptor densities were higher in salt-resistant than in salt-sensitive Dahl and Sabra rats. In contrast, renal alpha 2-adrenoceptor density was higher in salt-sensitive than in salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between Dahl and Sabra substrains. Noradrenaline content in cerebral and renal cortex were also similar in both these rat substrains. Sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in salt-sensitive but not in salt-resistant rats. Cerebral and renal alpha 1-adrenoceptor densities were unchanged in salt-sensitive and salt-resistant substrains of Dahl and Sabra rats. In addition, sodium ions reduced the affinity of adrenaline for renal alpha 2-adrenoceptors in salt-sensitive rats but not in salt-resistant rats. We can conclude that there exist genetically determined differences in the densities and properties of cerebral and renal alpha 2-adrenoceptors between salt-sensitive and salt-resistant rat strains. Abnormal densities of alpha 2-adrenoceptors may play a primary role in the role in the development of hypertension in salt-sensitive animals. These results also suggest an association between absence of sodium regulation of alpha 2-adrenoceptors and resistance to salt-induced hypertension. The absence of sodium regulation in salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the receptor system. This property may represent a genetically-mediated change responsible for the resistance to the development of salt-induced hypertension.

Interaction of clonidine and rilmenidine with imidazoline-preferring receptors.

In the present study the imidazoline radioligand 3H-RX 781094 (idazoxan) was used to characterize the alpha 2-adrenergic receptors in basolateral membranes of rabbit proximal tubule. Scatchard analysis of equilibrium binding data showed that 3H-RX 781094 labels 566 +/- 118 fmol/mg protein of binding sites with an apparent dissociation constant (Kd) of 1.45 +/- 0.14 nmol/l. However, in competition studies, only 25% of the 3H-RX 781094 binding was inhibited by catecholamines and alpha 2-adrenergic compounds; the remaining 75% of specific binding was inhibited only by molecules having an imidazoline or oxazoline ring with the following order of potency: cirazoline greater than tolazoline greater than UK 14 304 greater than rilmenidine greater than clonidine. These data suggest that imidazoline compounds bind to both alpha 2-adrenergic receptors and to a 'non-adrenergic site' which might be defined as an imidazoline-preferring receptor. Based on these results, it is possible to hypothesize that imidazoline and oxazoline drugs, such as clonidine and rilmenidine, exert their hypotensive activity partly through the stimulation of imidazoline receptors.

Alpha-adrenoceptors in Dahl hypertensive and normotensive rats: effect of sodium.

Sodium ions play an important role in vitro and in vivo in the regulation of alpha 2-adrenoceptors. The in vitro effect of sodium on cerebral and renal alpha-adrenoceptors was investigated in Dahl salt-sensitive and salt-resistant rats. Cerebral alpha 2-adrenoceptor densities were higher in Dahl salt-resistant rats. In contrast, the renal alpha 2-adrenoceptor density was higher in Dahl salt-sensitive than in Dahl salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between the two types of rat. Noradrenaline contents in the cerebral and renal cortex were also similar in these two rat substrains. An influx of sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in Dahl salt-sensitive but not in Dahl salt-resistant rats. Under these conditions alpha 1-adrenoceptor densities remained unchanged. The absence of sodium regulation in Dahl salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the alpha 2-adrenoceptor system. We conclude from the present study that there are marked differences in density and in the role of sodium regulation of cerebral and renal alpha 2-adrenoceptors from salt-sensitive and salt-resistant Dahl rats. These differences may play a primary role in the resistance or in the sensitivity of salt-induced hypertension.

Evidence for non-adrenergic binding sites for [3H]idazoxan in the smooth muscle of rabbit urethra.

The binding characteristics of [3H]idazoxan and [3H]rauwolscine, two potent alpha 2-adrenoceptor antagonists, were compared in the rabbit urethral smooth muscle. The maximal binding capacity was 6 times higher for [3H]idazoxan than for [3H]rauwolscine in male rabbits. No difference was observed for these radioligands in female rabbits. There were marked differences in the ability of alpha 2-adrenergic compounds to inhibit [3H]idazoxan and [3H]rauwolscine binding. These results were consistent with the existence of non-alpha 2-adrenoceptor sites for [3H]idazoxan in the rabbit urethral smooth muscle.