REDUCED α₁‐ADRENORECEPTOR MEDIATED RESPONSIVENESS IN VAS DEFERENS FROM SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

alpha-adrenoreceptor-mediated responses were investigated in isolated vasa deferentia from spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY) and normotensive rats (NWR). There was no significant difference between NWR, WKY and SHR in the inhibition of the isometric contraction to single pulse field stimulation by the alpha 2-selective agonist xylazine in prostatic portions, nor by xylazine and the alpha 1-selective agonist amidephrine in epididymal portions in the presence of nifedipine to prevent postjunctional actions of alpha 1-selective agonists. There was no significant difference between NWR, WKY and SHR in the potency of amidephrine in causing a postjunctionally mediated potentiation of the isometric contraction to single pulse field stimulation in prostatic portions but the maximum potentiation was significantly reduced in SHR. However contraction by the calcium entry facilitator, Bay K 8644, was not significantly different between NWR, WKY and SHR. The maximum direct contraction to amidephrine, but not to Bay K 8644, was also significantly reduced in SHR. It is concluded that the altered alpha 1-adrenoreceptor-mediated responsiveness in SHR is due not to genetic strain, but is presumably linked to development of hypertension.

Enhanced noradrenergic transmission in the spontaneously hypertensive rat anococcygeus muscle

“…This is supported by several studies in vas deferens that show essentially that nerve‐mediated responses are larger in SHR. A substantial part of transmission in the vas is purinergic, and this component has been shown to be enhanced (Docherty & Warnock, 1986; Guitart et al , 2002 ) providing further support for a fault in the transmitter release process. In anococcygeus, responses to EFS have an NPY component ( Hoyo et al , 2002 ), so it cannot be assumed that the mechanism here is purely ‘adrenergic’.…”

“…Since the eponymous characteristic of the SHR is a feature associated with peripheral resistance, and hence by implication with control of arterial vascular smooth muscle, it is logical to seek an explanation there. There is no question that in SHR the smooth muscle in several tissues is aberrant ( Altman et al , 1977 ; Docherty & Warnock, 1986; Muir & Wardle, 1989; Katzuragi et al , 1991 ; Marin, 1993; Vila et al , 1993 ; Tabernero et al , 1996 ; Vivas et al , 1997 ). It may be that the combination of a sympathetic transmission defect and variable excitability of smooth muscle has produced complicated experimental data that has frustrated the attainment of a simple consensus.…”

“…The possibility that the key primary defect lies in sympathetic transmission rather than in a specifically vascular effect was investigated by studying the responses of nonvascular tissues of SHR. Altered responsiveness was found in smooth muscle such as stomach ( Altman et al , 1977 ) and vas deferens (Docherty & Warnock, 1986; Katzuragi et al , 1991 ; Vivas et al , 1997 ). However, there were also negative observations, two of which utilised noradrenaline's contractile response in the anococcygeus muscle of SHR (Laher & Triggle, 1984a) or Dahl hypertensive rats (Laher & Triggle, 1984b; Lee et al , 1987 ).…”

Adrenergic and purinergic components in bisected vas deferens from spontaneously hypertensive rats

“…Similarly, previous studies on SHR and WKY rat vas deferens were also carried out in whole vas (Caufield et al ., 1977; Katsuragi et al ., 1991; Caricati‐Neto et al ., 1992). However, comparison of the two ends of the organ has been performed to further study modifications due to hypertension (Sakai et al ., 1984; Docherty & Warnock, 1986; Vivas et al ., 1997). The existence of an adrenergic and a non‐adrenergic component in the biphasic contractile response in both halves of the rat vas deferens, therefore, needs further studies to set their relative contribution to the modified contractile response in hypertensive animals.…”

“…These facts could indicate a general alteration of the smooth muscle function in SHR possibly related to modi®cations in a 1 -adrenoceptors (Mulvany, 1988). An increase (Cau®eld et al, 1977;Caricati-Neto et al, 1992;Vivas et al, 1997), no modi®cation (Corbett et al, 1980;Sakai et al, 1984) and even a decrease (Docherty & Warnock, 1986) in postjunctional a 1 -adrenoceptor mediated responses are reported in vas deferens from SHR. On the other hand, an enhanced purinergic contribution to the co-transmission process has been described in the SHR isolated tail artery (Vidal et al, 1986) as compared to WKY.…”