The purpose of this study was to determine the heart rate and arterial blood pressure changes to isometric skeletal muscle contraction and muscle stretch before and after microinjecting an antagonist to substance P (SP) or somatostatin (SOM) into the L-7 dorsal horn region of the spinal cord of anesthetized cats. Anesthesia was induced by administering an anesthetic gas mixture and was subsequently maintained with α-chloralose. Triceps surae contraction was induced by electrically stimulating the L-7 ventral root. Three muscle manipulations (all 1 minute in duration) were performed: 1) continuous tetanic contraction, 2) intermittent tetanic contractions (1 second of contraction, 1 second of relaxation), and 3) passive muscle stretch. Saline microinjections had no effect on the cardiovascular responses to these muscle manipulations. However, both peptide antagonists blunted the pressor response to a continuous tetanic contraction as mean arterial pressure increased 47±4 and 44±4 mm Hg before and 28±3 and 28±4 mm Hg after microinjecting the SP or SOM antagonist, respectively. In contrast, neither antagonist influenced the increase in mean arterial pressure produced by passive stretch; values were 43±6 versus 41±6 mm Hg (SP antagonist) and 39±7 versus 42±7 mm Hg (SOM antagonist) before and after injections, respectively. Microinjecting the SOM antagonist attenuated the pressor response to intermittent tetanic contractions (44±4 mm Hg before SOM antagonist versus 26±4 mm Hg after SOM antagonist), whereas the SP antagonist had no effect (35±3 mm Hg before SP antagonist versus 32±4 mm Hg after SP antagonist). These data suggest that the spinal release of SP and SOM plays a role in eliciting the cardiovascular responses to isometric muscle contraction. Furthermore, the release of these peptides appears to be the result of activation of contraction, not mechanically sensitive muscle afferents.