α-Adrenoceptors of aortae from genetically hypertensive rats: reaction with 2-halogenoethylamines

Abstract

The responses of aortic rings from adult spontaneously hypertensive and Carworth normotensive Wistar rats to noradrenaline were compared. The former developed slightly more tension at low, and markedly less tension at high concentrations (> 10−8m) of noradrenaline. The α‐adrenoceptors of these tissues were probed using 2‐halogenoethylamines to compare quantitatively α‐adrenoceptors in normotensive and hypertensive tissue. The kinetics of the recovery of response to noradrenaline from the short‐lived antagonism produced by NN‐dimethyl‐2‐bromo‐2‐phenylethylamine were identical in aortae from both strains of rat. The rate of recovery of response was the same as the rate of loss of tritium from the tissues, suggesting the absence of spare receptors in rat aorta. An estimation of the number of α‐adrenoceptors in aortic tissue did not show a difference between normotensive and hypertensive tissues. Evidence is presented that 2‐halogenoethylamines react at two kinetically distinguishable sites in rat aorta. The rates of return of response to noradrenaline after receptor blockade with N‐(2‐bromoethyl)‐N‐ethyl‐N‐1‐naphthylmethylamine (SY‐28) in tissues pretreated with NN‐dimethyl‐2‐bromo‐2‐phenylethylamine were the same in aortic smooth muscle from both strains of rat. No significant difference was found in the reactions of 2‐halogenoethylamine α‐adrenoceptor antagonists in aortic tissue from either strain of rat.

The action of diazoxide analogs on aortic reactivity in normotensive and spontaneously hypertensive rats

“…subsequent step in the activation process, but Rhsdes and Sutler ( 197 1 ), found diazsxide to be a noncompetitive antagonist of NA in the rabbit mesenteric vein. Similarly, Janis and Triggle ( 1973) reported diazoxide to be a noncompetitive antagonist towards NA, potassium, calcium-NA, and ca1ciun.a-psaassiurrm responses in both nosmotensive and hypertensive rat aortae.…”

“…5-9 ; For personal use only. Since diazoxide (and its analogs) antagonizes the responses to several vasoconstrictor agents including NA, calcium, barium, 5-hydroxytryptamine, and potassium (Wohl et al 1967(Wohl et al , 1968n, 1968bMcNeill et al 1969;Rhodes and Sutter 1971 ;Janis and Triggle 1973), it has been argued that its action is not at a specific receptor but rather is at some site(s) that is a common component of receptor systems, possibly a site involved in the mobilization of calcium for excitation-contraction coupling (Janis and Triggle 1973). Direct competition between diazoxide and calcium as the basic mechanism of action seems unlikely in view of the evidence presented here and previously (Janis and Triggle 1973) that diazoxide and its analogs act noncompetitively against calcium-induced responses.…”

“…As a hypotensive agent, it is more ef-site activated by NA a-receptors) in mediating fective in hypertensive than in normotensive vasoconstriction, and that this site might be animals f~u b i n et 1962; Stanton and the precise locus of the vascular derangement 1 9 6~; Neuvonen 1971 ), and Wohl in hypertension. Other studies have also sug-(1 96ga) found diazoxide to be more gested the existence of a calcium site as a cornin antagonizing barium-induced contractions of POnent of the a-receptor (Swamy and Triggie 197%;Triggle 1972). Although Wohl diazoxide against NA-induced responses in aortae from SWW of the Japanese strain (Okamots and Aoki 1963).…”

“…The animals were 15-17 weeks old and had blood pressures of 115 & 3.69 and 192 9 3.13 mmHg for C F N and SMR ( n = 25), respectively. Systolic blood pressures were recorded from the tails of unanesthetized rats with a pneumatic pulse transducer and electrophysmograph as previo~~sly described (Janis and Triggle 1972). Three determinations of blood pressure were made on each rat.…”