Adela Sánchez

Dietary sodium regulation of blood pressure and renal α1- and α2- receptors in WKY and SH rats☆

Abstract We studied the effect of high (8%) versus normal (0.6%) sodium diet on renal α1 and α2-adrenergic receptors and on blood pressure in Okamoto-Aoki spontaneously hypertensive (SH) and Wistar Kyoto (WKY) “normotensive” rats. SH rats had higher renal α1 (p .01). Ingestion of the high salt diet for 5 weeks increased blood pressure from 130 mmHg to 174 mmHg (p

Dietary Sodium and Renal α2-Adrenergic Receptors in Dahl Hypertensive Rats

Dahl sodium-sensitive and resistant rats were fed low and high sodium diets. Renal plasma membrane α2-adrenergic receptor concentrations were greater (p<.05) in sensitive than in resistant rats while ingesting a low sodium diet. On a high sodium diet the α2 receptor concentration increased (p<.01) in sensitive but not in resistant rats. Since α2 receptors are located in proximal tubules at sites where nor-epinephrine induces sodium reabsorption, we postulate that this genetically determined abnormal receptor regulation could lead to exaggerated sodium retention and possibly high blood pressure.

Age-Related Changes of Norepinephrine Content in Kidneys of Spontaneously Hypertensive and Wistar-Kyoto Rats

Renal norepinephrine (NE) content was determined during the development of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats in an attempt to correlate biochemical changes with the reported functional changes occurring in hypertension development in the SHR. In contrast to WKY rats, in which the levels of NE remained relatively constant with age, renal NE content in the SHR was highest at the 4th week of age, decreasing transiently during the 5th, 6th, and 7th weeks, and then again reaching a plateau during the 8th week. The fall in NE content in the kidney is associated with a rise in blood pressure with age in SHR and suggests a relationship between NE levels and hypertension.

Effect of prazosin and yohimbine on systolic blood pressure and on renal norepinephrine content in Doca-salt rats

We studied the effect of alpha-1 and alpha-2 blockers (prazosin and yohimbine) on systolic blood pressure (SBP) and on renal norepinephrine (NE) content in Sprague-Dawley normotensive and DOCA-salt rats. The administration of desoxycorticosterone acetate (DOCA) to these rats for 6 weeks increased their SBP from 137 to 183 mmHg (p less than .001). This increase was prevented by simultaneous administration of prazosin (p less than .001), yohimbine (p less than .01), or prazosin + yohimbine (p less than .001). DOCA rats on saline and on yohimbine had lower renal NE content (p less than .05 and p less than .001, respectively) than normotensive rats. Renal NE content of DOCA rats on yohimbine decreased with respect to those treated with prazosin (p less than .001) or prazosin + yohimbine (p less than .05). Besides, renal NE content of DOCA rats on prazosin increased when compared to control DOCA rats (p less than .05). However, these drugs showed no effect on SBP and on renal NE content in normotensive rats. These findings further confirm that the alpha adrenoceptor blockade can prevent the hypertension of DOCA-salt rats in such a way that their blood pressure stabilizes at similar levels to those observed in normotensive treated animals.

Altered renal α-adrenoceptor density induced by prolonged NaCl and DOCA administration in spontaneously hypertensive rats

This study examines the effects of a 6-week exposure to 1% NaCl in tap water with and without desoxycorticosterone acetate (DOCA) on renal a adrenoceptors and systolic blood pressure (SBP) in spontaneously hypertensive adult rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. On normal sodium intake, SHR had higher renal α1- (p < 0.05) and α2-adrenoceptor densities (p < 0.001) and SBP (p < 0.001) than WKY rats. Although WKY rats given either 1% NaCl, DOCA, or DOCA plus 1% NaCl developed hypertension after 6 weeks of treatment, only 1% NaCl administration for the same period produced an increase in the α1-adrenoceptor density when compared to the control (p < 0.001). In SHR, ingestion of 1% NaCl or DOCA plus 1% NaCl increased the already elevated α2-adrenoceptor density (p < 0.001) and SBP even more in this strain after 6 weeks of treatment. Equilibrium dissociation constants (Kd), however, were similar for both classes of receptors in experimental and control rats. The results of this study indicate that only the combination of 1% NaCl in tap water and DOCA administration is effective in accelerating hypertension in adult SHR. On the other hand, in this form of genetic rat hypertension, exaggerated sodium intake with or without DOCA administration could presumably be correlated with the increased renal α2 adrenoceptors observed in these animals.

Altered renal α-adrenoceptor regulation in DOCA-salt rats: chronic effects of α1- and α2-receptor blockers

Abstract Effects on the α-adrenoceptor binding in the kidneys of DOCA-salt rats were examined after a 6 week treatment of once-daily injections of prazosin, a selective α 1 - adrenoceptor blocker; yohimbine, a selective antagonist for α 2 - adrenoceptors ; and prazosin plus yohimbine. α 1 - Receptor binding was decreased by prazosin, while α 2 - receptor binding was increased by simultaneous administration of prazosin + yohimbine. Equilibrium dissociation constants (K D ) for [ 3 H]prazosin and [ 3 H]yohimbine were not significantly different (between groups). Since these drugs can prevent the development of hypertension in DOCA-salt rats, the present data strongly suggests that selective alteration of α-receptor-mediated physiological responses is unrelated to decreased or increased binding site densities. The mechanism of hypertension prevention may involve changes in the coupling of receptors to postreceptor events.